Vaccines Against Malaria [1 ed.] 9780309571500

Citation preview

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

i

Vaccines Against Malaria: Hope in a Gathering Storm

Committee on Malaria Vaccines Board on International Health Board on Health Promotion and Disease Prevention INSTITUTE OF MEDICINE

Philip K. Russell and Christopher P. Howson, Editors

NATIONAL ACADEMY PRESS Washington, D.C. 1996

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

ii NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competencies and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. This study was supported in part by the MacArthur Foundation, the Rockefeller Foundation, the Burroughs Wellcome Fund, the National Institutes of Health, and the Navy Medical Research Institute. The views presented in this report are those of the Committee on Malaria Vaccines and are not necessarily those of the funding organizations. Additional copies of this report are available in limited quantities from: Board on International Health Institute of Medicine 2101 Constitution Avenue, N.W. Washington, DC 20418 Copyright 1996 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

iii

COMMITTEE ON MALARIA VACCINES PHILIP K. RUSSELL (Chair), Department of International Health, School of Hygiene and Public Health, Johns Hopkins University STANLEY O. FOSTER, Department of International Health, Rollins School of Public Health, Emory University MAURICE R. HILLEMAN,* Institute for Therapeutic Research, Merck Research Labs, West Point, Pennsylvania RUSSELL J. HOWARD, AFFYMAX Research Institute, Santa Clara, California JEFFREY V. RAVETCH, Sloan-Kettering Institute, New York HARRISON C. SPENCER, London School of Hygiene and Tropical Medicine, University of London Staff CHRISTOPHER P. HOWSON, Project Director KIMBERLY A. BREWER, Research Assistant DELORES H. SUTTON, Project Assistant STEPHANIE Y. SMITH, Project Assistant MICHAEL A. STOTO, Director, Division of Health Promotion and Disease Prevention KATHLEEN R. STRATTON, Associate Director, Division of Health Promotion and Disease Prevention MONA R. BRINEGAR, Financial Associate

*Member, National Academy of Sciences.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

iv

BOARD ON INTERNATIONAL HEALTH BARRY R. BLOOM (Cochair),* Howard Hughes Medical Institute, Albert Einstein College of Medicine, Yeshiva University HARVEY V. FINEBERG (Cochair),* Harvard School of Public Health JOHN H. BRYANT,* Moscow, Vermont JACQUELYN CAMPBELL, The Johns Hopkins University School of Nursing RICHARD G. A. FEACHEM, London School of Hygiene and Tropical Medicine, University of London JULIO FRENK,* Fundación Mexicana para la Salud, San Jerónimo Líce, Mexico DEAN JAMISON,* University of California, Los Angeles EILEEN T. KENNEDY, Center for Nutrition Policy and Promotion, Washington, D.C. ARTHUR KLEINMAN,* Harvard Medical School WILLIAM E. PAUL,* National Institute of Allergy and Infectious Diseases and Office of AIDS Research, National Institutes of Health, Rockville, Maryland PATRICIA ROSENFIELD, The Carnegie Corporation of New York, New York City THOMAS J. RYAN, Boston University School of Medicine and Boston University Medical Center SUSAN C. M. SCRIMSHAW,* University of Illinois School of Public Health, Chicago JUNE E. OSBORN (Institute of Medicine Liaison),* The University of Michigan School of Public Health WILLIAM H. FOEGE (Ex Officio),* Carter Center, Emory University DAVID P. RALL (Institute of Medicine Foreign Secretary ),* National Institute of Environmental Health Sciences (retired), Washington, D.C. Staff CHRISTOPHER P. HOWSON, Director KIMBERLY A. BREWER, Research Assistant STEPHANIE Y. SMITH, Project Assistant MONA R. BRINEGAR, Financial Associate

*Member, Institute of Medicine.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

v

BOARD ON HEALTH PROMOTION AND DISEASE PREVENTION DONALD R. MATTISON (Chair), University of Pittsburgh M. JOYCELYN ELDERS, University of Arkansas for Medical Sciences, Little Rock DOUGLAS C. EWBANK, University of Pennsylvania CLAIRE M. FAGIN,* University of Pennsylvania PAUL S. FRAME,* Tri-County Family Medicine, Cohocton, New York ROBERT E. FULLILOVE, Columbia University School of Public Health KRISTINE M. GEBBIE,* Columbia University School of Nursing JEAN GOEPPINGER, University of North Carolina, Chapel Hill ANTONIO M. GOTTO, Jr.,* The Methodist Hospital, Houston ELLEN R. GRITZ, M. D. Anderson Cancer Center, The University of Texas, Houston RUTH T. GROSS,* Stanford University (retired), Longboat, Florida RICHARD B. JOHNSTON, Jr., The March of Dimes Birth Defects Foundation, White Plains, New York MARIE McCORMICK, Harvard School of Public Health RICARDO F. MUÑOZ, University of California at San Francisco and San Francisco General Hospital ELENA O. NIGHTINGALE,* Scholar-in-Residence, National Academy of Sciences, Washington, D.C. DIANA B. PETITTI, Kaiser Permanente Medical Care Program, Pasadena, California HUGH H. TILSON, Glaxo Wellcome Company, Research Triangle Park, North Carolina ROBERT B. WALLACE, University of Iowa Cancer Center KENNETH E. WARNER, University of Michigan School of Public Health ROBIN WEISS, Private Practice in Psychiatry, Baltimore, Maryland DONALD WHORTON, Private Practice, Alameda, California Staff MICHAEL A. STOTO, Director, Division of Health Promotion and Disease Prevention CYNTHIA ABEL, Program Officer DONNA THOMPSON, Division Assistant

* Member, Institute of Medicine

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

vi

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

ACKNOWLEDGMENTS

vii

Acknowledgments

The committee is grateful to the many individuals who made substantive and productive contributions to this project. Particular thanks are in order to the following workshop presenters, whose effective efforts provided important information bearing on the topic of this report: W. R. Ballou, Walter Reed Army Institute of Research Center; William Bancroft, U.S. Army Medical Research and Materiel Command; Ian Bathurst, LXR Biotechnology; W. Neal Burnette, Molecular Pharmaceutics Corporation; Graham Brown, The Walter and Eliza Hall Institute of Medical Research; Daniel Colley, Centers for Disease Control and Prevention; Michael Davies, Medical Research Council; Carter Diggs, U.S. Agency for International Development; Howard Engers, World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases; Kenneth Guito, Connaught Laboratories; Lee Hall, National Institute of Allergy and Infectious Diseases; Stephen Hoffman, Naval Medical Research Institute; Palle Jakobsen, Danish International Development Agency (DANIDA) and Commission of European Communities; David Kaslow, National Institute of Allergy and Infectious Diseases; Wenceslaus Kilama, National Medical Research Council of Tanzania and the African Malaria Vaccine Testing Network; Donald Krogstad, Tulane University School of Public Health and Tropical Medicine; Louis Miller, National Institute of Allergy and Infectious Diseases; Ruth Nussenzweig, New York University Medical Center; Adeoye Olukotun, BristolMyers Squibb Company; Jerald Sadoff, Merck Research Laboratories; and John Tine, Virogenetics Corporation. In addition, the committee is indebted to the following persons for their substantive contributions to the workshop: Finley Austin, Burroughs Wellcome Fund; Constance Carrino, U.S. Agency for International Development; Salvatore Cirome, Office of the Assistant Secretary of Defense; Mary Galinski, The Malaria Foundation, Inc.; Charles Hoke, Jr., Walter Reed Army Institute of Research; Stephanie James, National Institute of Allergy and Infectious Diseases; Surayanarayan Ramachandran, Fogarty International Center for Advanced Study in the Health Sciences; Barry Silverman, Cambridge Consulting Company; and John Tomaro, U.S. Agency for International Development. The committee also owes special thanks to Donald Krogstad for ensuring the completeness and accuracy of Chapter 2, and to Michael Katz, The March of Dimes, and Robert Eisinger, NIH Office of AIDS Research, for providing helpful background information for the report.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

ACKNOWLEDGMENTS

viii

The committee expresses its appreciation to the IOM staff who facilitated its work: Christopher Howson, study director; Kimberly Brewer, research assistant; Delores Sutton, project assistant; Stephanie Smith, project assistant beginning May 1996; Mona Brinegar, financial associate; Michael Edington, managing editor; and Claudia Carl, administrative associate. The committee also thanks Michael Stoto, director, and Kathleen Stratton, associate director, Division of Health Promotion and Disease Prevention, for their substantive input into the project and report, and Gregory Pearson, for his vision and hard work in realizing this project. This project was funded by the MacArthur Foundation, the Rockefeller Foundation, The Burroughs Wellcome Fund, the U.S. Public Health Service, and the Naval Medical Research Institute of the Department of Defense. The committee and staff are deeply appreciative of their support.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

CONTENTS

ix

Contents

1

Summary Project Charge Organization of the Report Findings and Recommendations

1 1 2 2

2

Malaria: The Deteriorating Situation Global Extent, Causative Agent, and Mode of Transmission of Malaria Health Impact of Malaria on the U.S. Population Economic and Development Impact of Malaria Current Strategies for Malaria Control The Rationale for Developing a Malaria Vaccine Goals and Target Populations for Malaria Vaccines

6 6 7 7 8 9 9

3

Malaria Vaccines: The Elements for Success Are Moving into Place

11

4

Current Obstacles to Development The Science Coordination

15 15 16

5

Solutions for Science

17

6

Solutions for Coordination Prerequisites for Success Models for Coordination and Leadership Implementing Coordination The Next Steps

19 20 21 21 23

References

24

Appendix: Workshop Agenda

27

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. CONTENTS

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

x

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SUMMARY

1

1 Summary

Malaria, which had been eliminated or effectively suppressed in many parts of the world, is undergoing a resurgence. It is a public health problem today in more than 90 countries inhabited by some 2,400 million people—40 percent of the world's population. Malaria is estimated to cause up to 500 million clinical cases and 2.7 million deaths each year (WHO, 1996). Every 30 seconds, a child somewhere dies of malaria. The global effects of the disease threaten public health and productivity on a broad scale and impede the progress of many countries toward democracy and prosperity (Oaks et al., 1991). The United States is not immune to the growing threat of malaria (Lederberg et al., 1992). The increasing number of U.S. citizens traveling and residing abroad, including military personnel, are at growing risk of serious disease and death from malaria. In addition, the toll of the disease in the developing world restricts regional economic development and impedes development of global markets for U.S. goods and services. The outlook for malaria control in the face of this deteriorating situation is grim. The continuing emergence of drug resistance in the malaria parasite and the widespread insecticide resistance of the mosquitoes responsible for transmitting the disease have reduced the selection of tools to control malaria— there are fewer options available now than there were 20 years ago. There is widespread agreement, however, that vaccines against malaria would be a cost-effective public health tool to reduce the burden of disease and will be an essential component of successful control of the global threat. The impressive strides made in the field of malaria research in the past 15 years provide compelling reasons to believe that a malaria vaccine is a biotechnological and immunological possibility. In spite of growing scientific optimism, however, the pace of vaccine development appears to be slowing because of diminishing public funds, fragmented public sector efforts, and limited interest within the vaccine industry. PROJECT CHARGE In view of the deteriorating global malaria situation and the urgent need for new and effective control measures, the IOM was asked by a consortium of

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SUMMARY

2

U.S. federal and private sponsors to conduct a workshop to evaluate current international efforts in malaria vaccine research and development and to make recommendations on how the U.S. federal government can help expedite more rapid and efficient development of promising malaria vaccine candidates. To accomplish this task, the IOM convened the Committee on Malaria Vaccines, a group of six members reflecting a broad range of expertise in microbiology, parasitology, vaccine research and development, molecular biology, epidemiology, and the conduct of vaccine field trials and related issues. The committee met on 7 July 1995 to review the project charge and develop the agenda for the international workshop. The workshop, which was subsequently held on 19–20 October 1995 in Washin, D.C. (see the Appendix for the agenda), addressed two key questions: what are the current incentives and disincentives to fuller participation of the industrial sector in malaria vaccine development, and how can the U.S. federal and industrial sectors and the international community work together more efficiently toward the common goal of developing effective malaria vaccines? This report summarizes the findings of the 19–20 October 1995 workshop. ORGANIZATION OF THE REPORT The report contains six chapters and one appendix. Chapter 1 summarizes the findings and recommendations of the workshop. Chapter 2 provides an overview of the global extent, causative agents, and mode of transmission of malaria; the health impact of malaria on the U.S. population; the economic and developmental impact of malaria; current strategies for malaria control; the rationale for developing a malaria vaccine; and the goals and target populations of malaria vaccine efforts to date. Chapter 3 focuses on the scientific and organizational elements that are in place and provides a rationale and basis for accelerated malaria vaccine development. Chapter 4 describes the current scientific and organizational obstacles that need to be addressed in developing a coherent plan of action, and Chapter 5 and Chapter 6 offer ways to surmount these obstacles. The Appendix provides the workshop agenda. FINDINGS AND RECOMMENDATIONS Workshop participants agreed that the successful development and widespread application of a vaccine that can prevent the illness and death of malaria could be one of the most important advances in medicine, with the potential for improving the lives of hundreds of millions of people. The successful completion of this task, however, will require an extraordinary level of effort in the scientific, public health, and industrial sectors, as well as coordination of these efforts. The following findings and recommendations of

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SUMMARY

3

the Committee on Malaria Vaccines are based on the evidence and testimony presented at the October workshop and are offered as a basis for coherent and focused action. Findings • Malaria is the most prevalent vector-borne disease in the world. It causes up to 500 million clinical cases each year. Given the importance of malaria and the shortcomings of antimalarial drugs and vector control, vaccine development merits a high priority. • A malaria vaccine is feasible. Malaria research over the past two decades has produced a compelling body of evidence demonstrating protective immunity in small animals, primates, and man. Antigens potentially involved in protective immunity have been identified in all stages of the life cycle of the malaria parasite. Although thus far it has proved difficult to elicit solidly protective vaccine immunity, related research on vaccine delivery and adjuvants, in conjunction with advances in malariology, provide the rational basis for a new, accelerated vaccine development effort. • An effective malaria vaccine will most likely consist of multiple genes/ antigens and a novel adjuvant or delivery system. It will likely require multiple sophisticated and proprietary technologies, which must be accessible for public sector use, while protecting industry's return on investment. • Two types of vaccines are envisioned, each with different characteristics and prospects for development. The first vaccine is needed to provide long-term protection against disease and to reduce mortality among children in endemic areas of the world. The second vaccine is needed to induce shorter-term, but highly protective, immunity in nonimmune adult travelers entering highly malarious (endemic) areas. • Successful development of malaria vaccines will require the collaborative efforts of government, academia, and industry. Each sector has unique capabilities to contribute, but the public sector must take the lead, given the costs of vaccine research and development and present beliefs that expected returns on investment will cover only a portion of the research and development outlay. The pharmaceutical and biotechnology industries must play a major role in resolving technical issues relating to appropriate expression and purification of antigens, vaccine formulation, and manufacturing technology, but new industrial development efforts will come only in conjunction with a successful, coordinated public sector effort that first proves the feasibility and value of a given technical approach. • A coordinated strategy for vaccine development, focusing on a limited number of development options, is essential. The high cost of producing and testing an experimental vaccine mandates a focus on a limited number of the most promising vaccine candidates.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SUMMARY

4

• Testing a successful malaria vaccine in the field can be readily accomplished and is no more difficult than the field testing required for most other vaccines against infectious agents. Mechanisms such as the African Malaria Vaccine Testing Network are currently in place to allow field trials to be conducted in an efficient and cost-effective manner in areas of high endemicity. • Market forces for developing malaria vaccines are potentially vigorous and are growing on a global scale, but they are not yet fully appreciated or understood. For potential industrial developers to make appropriate decisions or choices, analyses of potential markets for each type of potential vaccine candidate must be undertaken, and the results made widely available to interested parties in all involved sectors. Recommendations • A federal “Malaria Vaccine Development Board” should be established and given the responsibility, authority, and resources to carry out the strategy or strategies most likely to result in accelerated, successful The board should include development of malaria vaccines. representatives from academia, relevant federal government agencies, pharmaceutical and biotechnology companies, and foundations. A crucial initial task of the board would be to identify and focus U.S. development efforts on a limited number of the most promising malaria vaccine candidates. The board should monitor progress in malaria vaccine development in both the public and private sectors; identify development needs, opportunities, and priorities and advise interested parties and funding agencies of these findings; provide financial and other support for highpriority development efforts; and encourage collaboration among academia and private and public sector entities. To succeed, the board must have the following attributes: 1. access to sufficient resources to fill gaps in the malaria vaccine development process in a timely manner; 2. a sustained, long-term commitment to malaria vaccine development; 3. the ability to access all phases of the malaria vaccine development process, through field implementation of immunization programs; 4. the flexibility to address rapidly changing needs, technologies, and priorities in the field of malaria vaccine development; 5. the ability to access, in a cost-effective manner, optimal technologies and developmental expertise in either the private or the public sector; and 6. the ability to provide the leadership in conducting U.S. malaria vaccine development efforts and in coordinating these with international academic researchers, corporations, and relevant organizations such as the

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SUMMARY

5

World Health Organization, the World Bank, the United Nations Development Programme, and the Commission of the European Communities. While there are historical precedents for aspects of the proposed Malaria Vaccine Development Board, none completely covers all of the facets described above. Some examples of precedents that may be examined for relevance to elements of the board include the 1941 Commission on Influenza of the Armed Forces Epidemiology Board, the National Task Force on AIDS Drug Development, and the National Foundation for Infantile Paralysis. • The board should commission independent market analyses to assess potential global markets—both private and public—for each of the types of malaria vaccine. These analyses should be conducted by country or region, both in the industrialized and developing world, and findings made available to the global vaccine industry.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA: THE DETERIORATING SITUATION

6

2 Malaria: The Deteriorating Situation

This introduction provides an overview of: (1) the global extent, causative agents, and mode of transmission of malaria; (2) the health impact of malaria on the U.S. population; (3) the economic and developmental impact of malaria; (4) current strategies for malaria control; (5) the rationale for developing a malaria vaccine; and (6) the goals and target populations of malaria vaccine efforts to date. GLOBAL EXTENT, CAUSATIVE AGENT, AND MODE OF TRANSMISSION OF MALARIA The global importance of malaria is immense. It is the most prevalent vector-borne disease in the world, threatening some 2,400 million people in more than 90 countries—40 percent of the world's population. Malaria is estimated to cause up to 500 million clinical cases and 2.7 million deaths each year. The vast majority of deaths occur among young children; other high-risk groups include pregnant women and nonimmune travelers, refugees, displaced persons, and laborers entering endemic areas. The causative agents in humans are four species of Plasmodium protozoa— P.falciparum, P. vivax, P. ovale, and P. malariae. Of these, P. falciparum accounts for the great majority deaths. Malaria is most frequently transmitted from human to human by the female Anopheles mosquito; about 60 species are possible vectors for the disease under natural conditions. Malaria can also be transmitted by blood transfusions from infected persons and through contaminated needles and syringes. Even blood donations from semi-immune persons without clinical symptoms may contain malarial parasites. In congenital malaria, infected mothers transmit parasites to their children before or during birth (Hoffman, 1996). Life-Threatening Complications of Malaria Cerebral malaria produces seizures and unresponsive coma (Warrell et al., 1990). These complications are most frequent among African children (with a peak incidence at 3–4 years of age), but they also occur in Southeast Asian children and among nonimmune adults. Although cerebral malaria has a substantial mortality, an

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA: THE DETERIORATING SITUATION

7

uncertain fraction of those who survive (approximately 10 percent) have persistent neurologic deficits at the time of hospital discharge (Carme et al., 1993). Thus, the long-term effects of cerebral malaria on central nervous system development and function (including the ability to learn) are important unresolved questions with major implications for global health and development. Severe malarial anemia produces hemoglobin levels of less than 5 grams per 100 milliliters of blood—less than one-third the normal hemoglobin (Warrell et al., 1990). Although severe malarial anemia is widely prevalent until age 3, its peak incidence occurs around 6– 7 months of age (Marsh, 1992; Miller et al., 1994). Kidney failure is a common complication of malaria infection, and a major cause of death among nonimmune immigrants (Trang et al., 1992; Warrell et al., 1990; Weber et al., 1991). HEALTH IMPACT OF MALARIA ON THE U.S. POPULATION U.S. Travelers Abroad The importance of malaria for the U.S. military is enormous. In Vietnam, for example, nearly 10 percent of soldiers had the disease in late 1965, and attack rates for some units were as high as 60 per 100 soldiers each year. Overall, malaria was the most important cause of hospitalization other than combat wounds (Neel, 1973). Peace Corps volunteers also have intense malaria exposures. During the late 1980s, drug-resistant P. falciparum infection caused serious illnesses in approximately 1,600 Peace Corps workers in West Africa alone. Finally, tourists are at increasing risk, even with short-term exposure, as demonstrated by recent reports of transit passengers being infected with malaria while waiting on planes that were being refueled in West Africa (Isaacson, 1989; Lobel et al., 1993). Over 1,000 cases of malaria are known to occur each year in tourists returning to the United States. U.S. Resident Population Malaria transmission can occur in the United States. With the return of infected veterans after World War II, the Korean War, and the Vietnam War, and the arrival of infected Southeast Asian refugees, reports have confirmed transmission of malaria by indigenous anopheline mosquitoes to U.S. residents who had never left the country (Luby et al., 1967; Maldonado et al., 1990). ECONOMIC AND DEVELOPMENT IMPACT OF MALARIA When a substantial proportion of a country's population is ill with malaria for five or six months each year, sustained economic development is very difficult to achieve. Countries thus compromised cannot easily become active trading partners with the United States, nor are they positioned to decrease their dependence on

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA: THE DETERIORATING SITUATION

8

foreign aid. Similarly, when child survival is threatened by malaria and other infections diseases, family planning and environmental quality are simply not priorities. To address development and environmental issues on a global scale, one must first prevent death and disability from malaria and other childhood diseases in regions where death rates are high. CURRENT STRATEGIES FOR MALARIA CONTROL Drug-Based Control Strategies Although antimalarial drugs are necessary to prevent death and complications in severely ill patients, they are not sufficient for malaria control. Most developing countries recommend antimalarial treatment only for symptomatic infections, because treating all infections would produce relatively small health benefits in proportion to the cost, would exacerbate selection for drug-resistant parasites, and could impair the development and boosting of natural immune responses. Unfortunately, most antimalarials are now compromised by antimalarial resistance, including the aminoquinolines and their analogs—chloroquine, mefloquine, halofantrine, quinine, and quinidine—and the antifolates. Artemisinin offers a promising alternative approach because it is effective against P. falciparum, which is resistant to the older drugs, but there are unresolved questions about its potential neurologic toxicity (Brewer et al., 1994). Thus, antimalarial treatment is currently in disarray because of widespread drug resistance in the parasite throughout all regions endemic for malaria (Hoffman, 1996; Wernsdorfer, 1994). Vector-Based Control Strategies Because of growing antimalarial drug resistance in the parasite, more emphasis is being placed on vector control by health authorities. An important recent development is the use of insecticide-impregnated bednets and curtains. Bednets and curtains treated with insecticides such as permethrin have both insecticidal and repellent effects, and they may reduce the number of anopheline mosquitoes within houses by more than 95 percent (Doumbo et al., 1991). Their effect on the prevalence of infection has been less marked, however; several studies suggest a 40– 50 percent reduction in the prevalence of P. falciparum parasitemia (Beach et al., 1993). The impact of insecticide-impregnated bednets on mortality and the incidence of severe malaria is still uncertain and remains under study (Alonso et al., 1991; Mbogo et al., 1995). Recent reports suggest that insecticide-impregnated bednets reduce malaria mortality, but raise the possibility that their efficacy may be lower in areas with more intense transmission (Binka et al., 1996; Curtis, 1996; Nevill et al., 1996). Questions have been raised as to whether this strategy might selectively encourage the proliferation of anopheline mosquitoes that bite outside the home (and would therefore not be exposed to bednets), and whether it could shift the

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA: THE DETERIORATING SITUATION

9

malaria mortality currently observed among young children to older children and young adults. THE RATIONALE FOR DEVELOPING A MALARIA VACCINE The rationale for accelerated development of a malaria vaccine is based on the following observations: • Effective vaccines, as a group, represent the single most cost-effective public health intervention. • Current methods of malaria control have limited effectiveness. • Drug resistance is increasing. • Scientific advances in malaria immunology and advances in vaccinology have made the development of malaria vaccines an achievable goal. • Vaccines in conjunction with other measures could greatly improve the effectiveness of malaria control. GOALS AND TARGET POPULATIONS FOR MALARIA VACCINES The complex life cycle of the malaria parasite has complicated vaccine development efforts (see Hoffman 1996 for a description of the Plasmodium life cycle). Each parasite stage has different antigens that lead to protective immunity and immune responses effective against one stage (for example, sporozoites), but that generally have been ineffective against other parasite stages (such as the asexual and sexual stages). This has resulted in a rich diversity of approaches to malaria vaccine development and to multiple current vaccine candidates. Development efforts to date have focused on three vaccine types. Preerythrocytic Vaccines The rationale for a preerythrocytic malaria vaccine is to prevent bloodstream infection by stimulating an immune response to sporozoite, or liver-stage, antigens. Although these vaccines are seen to offer the best protection for nonimmune individuals such as children or foreign nationals, they may also be of value to semi-immune residents of endemic areas.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA: THE DETERIORATING SITUATION

10

Asexual Blood-Stage Vaccines The purpose of immunization with asexual blood-stage (merozoite) antigens is to control the magnitude of the asexual parasitemia, and thus decrease the incidence of severe disease. These vaccines are seen to be of most benefit to semi-immune, long-term residents of endemic areas, although they may also benefit nonimmunes. .

Sexual (Gametocyte) Vaccines These vaccines are directed toward blocking infection of mosquitoes. As a result, such vaccines would not have any effect on the clinical manifestations of malaria in an individual, but could have major impact through reducing malaria transmission, and thus malaria mortality and morbidity at the population (community) level.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA VACCINES: THE ELEMENTS FOR SUCCESS ARE MOVING INTO PLACE

11

3 Malaria Vaccines: The Elements for Success Are Moving into Place Despite the extraordinary economic and human toll exacted by malaria— and experimental evidence that an effective vaccine could be produced—funds for malaria vaccine development have been meager at best (see Hoffman, 1996, for a history of malaria vaccine development). The explanation for this discrepancy is complex, and includes the lack of a clear, coordinated strategy for vaccine development and the overall diminution of funds for global health activities. Thus, this chapter focuses on the scientific and organizational elements presented at the workshop that provide a basis for action. • Protection against malaria has been demonstrated in several rodent and primate models. Limited immunity against malaria has already been achieved with some vaccines in humans. Over the past 40 years, numerous studies in man and animal models using different parasite strains have shown that immunity against malaria can be achieved through immunization (Nussenzweig et al., 1967). Radiation-attenuated sporozoites, when injected by mosquitoes or by needle in large numbers, can induce complete protection against malaria infection in animals and in man for a year or more. While this cumbersome method is unsuitable for widespread immunization, synthetic vaccines based on a single antigen derived from this process have successfully protected a small proportion of immunized subjects. Immunity that reduces parasite replication in the liver and in the blood stages of the parasite has been convincingly demonstrated in animal models, and it is reasonable to expect that such immunity could modify infection, and thus prevent or modify disease in humans. Furthermore, an immune response that prevents transmission of the parasite by mosquitoes has also been demonstrated. Research on the molecular biology and immunology of malaria has identified many antigens expressed at different stages of the infection that may contribute to effective immunity. The opportunity now exists to select and combine the best antigens with the most promising vaccine formulation methods to induce effective, multifaceted defenses against the parasite. Workshop participants agreed that such a broad-based approach involving multiple antigens from multiple stages of the parasite will be required for the next generation of malaria vaccines. • Remarkable advances in vaccinology offer great potential for use in malaria vaccines.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA VACCINES: THE ELEMENTS FOR SUCCESS ARE MOVING INTO PLACE

12

Research on both malaria and other infections diseases has generated new approaches to immunization that offer great promise for malaria vaccines. Nucleic acid vaccines, proteosomes, and several new adjuvants are examples of technologies that may be appropriate for the next generation of malaria vaccines. • Market forces for developing malaria vaccines, while not appreciated, are potentially vigorous, and growing on a global scale. As with the development of any commercial product, a clearly identified market is essential. Remarkably little effort has been directed toward characterizing potential global markets for different malaria vaccines. The traditionally most attractive markets have been thought to be the military and “traveler” markets of North America and Europe—the vast emerging middle classes in South and Central America, Africa, India, and Southeast Asia, where the risk of malaria is widely recognized, have been largely overlooked. Nevertheless, the type of vaccine suitable for travelers, which may be quite expensive, could also find a vigorous and profitable market within these populations. It seemed likely to workshop participants that analyses of potential consumer populations would reveal a market of hundreds of millions of dollars annually, which would render a malaria vaccine an economically sound investment for a pharmaceutical company. The neediest populations, however, still comprise the poor and very large populations of Asia and Sub-Saharan Africa, which suffer disproportionate death and morbidity from malaria, yet have limited ability to pay for vaccines. Workshop participants recognized that a vaccine for reducing mortality in these populations, while potentially more feasible, must also be affordable. Large international agencies such as the World Health Organization, UNICEF, and the bilateral assistance agencies, which would be the most likely purchasers and distributors of vaccines for these populations, would have to do so through pricing and delivery agreements with vaccine manufacturers. Analyses of these markets, including cost-effectiveness studies of vaccine price supports compared with other methods of malaria prevention and control, are essential for informed decision-making by industry and the public sector. • Immunization-challenge studies in humans offer a means of rapid evaluation of efficacy for some types of malaria vaccines. Obtaining evidence of safety and efficacy in the target population is a critical step for any new vaccine candidate. Early in the development process, preerythrocytic and sexual-stage malaria vaccines can be safely tested for efficacy through experimental challenge of a small number of tightly controlled and monitored volunteers recruited under informed consent procedures. Such smallscale trials ensure that only the most promising vaccine strategies proceed to more elaborate and expensive field trials. The expertise and technical support required to perform this procedure are available in academic centers and in Department of Defense laboratories.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA VACCINES: THE ELEMENTS FOR SUCCESS ARE MOVING INTO PLACE

13

• Mechanisms are in place to allow field trials of malaria vaccines to be conducted in an efficient and cost-effective manner. Proving efficacy in definitive field trials is a critical milestone in the vaccine development process, and it can easily be the most expensive phase, particularly if many thousands of subjects must be studied to achieve sufficient statistical power. This is clearly not the case for malaria—there are numerous areas in which malaria attack rates approach 100 percent yearly. Highly significant results for an effective malaria vaccine can thus be achieved with relatively small, focused field trials. This has been effectively demonstrated by the three field trials of the experimental vaccine, Spf66, in Tanzania, The Gambia, and Thailand (Alonso et al., 1994; D'Alessandro et al., 1995).1 Many promising field sites have already been developed with international funding in anticipation of near-term testing of vaccine candidates. These and other sites in development could be overseen and monitored by an extensive global malaria network of experienced researchers, foundations, and nongovernmental organizations that are anxious to participate in the process and could contribute resources that would greatly diminish the financial risk of taking vaccine candidates to field trials. One such promising example is the African Malaria Vaccine Testing Network, which was assembled in 1995 to strengthen malaria vaccine research capability in Africa and to coordinate and standardize regional field trials of candidate vaccines (Hviid and Jakobsen, 1995). • Clear and important spin-off benefits of malaria vaccine research can be identified. The inherent complexity of the malaria parasite and the resulting immune response make it a natural target for cutting-edge fundamental and applied research. As a result, malaria vaccine research has historically been a leader in the development of new technologies with broad applicability to human health. For example, the world's first recombinant vaccine produced in bacteria and the first synthetic peptide vaccine to be tested in humans were malaria vaccines. The most complex vaccine yet devised, an attenuated bioengineered vaccinia vector expressing

1The efficacy of SPf66 has been evaluated recently in clinical trials carried out in SubSaharan Africa and Thailand. In Tanzanian children aged 1–5, the adjusted efficacy of SPf66 was estimated to be 31 percent (95 percent confidence intervals 0–52 percent; p < 0.05) in preventing clinical malaria (defined as fever and parasite density > 20,000parasites/µL blood) (Alonso et al., 1994). In infants in The Gambia who were 6–11 months of age at the time of first inoculation, the efficacy against first or only episodes of clinical malaria (defined as fever plus parasite density > 6,000 parasites/µL blood) was estimated to be 8 percent (95 percent confidence intervals 18–29 percent; p = 0.50) (D'Alessandro et al., 1995). Estimated efficacy against all episodes of clinical malaria was even lower, at 3 percent. A clinical trial of SPf66 carried out in children in Thailand was recently completed; the results are being analyzed, and should be available by late 1996.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

MALARIA VACCINES: THE ELEMENTS FOR SUCCESS ARE MOVING INTO PLACE

14

seven malaria genes (NYVAC-P7), is a malaria vaccine now undergoing testing in humans. Malaria vaccine research was also one of the first research domains to incorporate recent technology using plasmid DNA vectors. In addition, some of the most advanced adjuvant work has been driven by malaria vaccine research, and these agents are likely to be important components of vaccines against HIV/ AIDS, herpes, cancer, and other diseases. • Development of a malaria vaccine complements other important malaria control measures to limit the burden of disease in endemic regions. Although malaria vaccines offer the greatest hope for sustained protection for the largest number of people, workshop participants acknowledged that on a global scale, malaria vaccines should be considered as one arm of a multicomponent malaria prevention and control strategy that includes mosquito control programs, the use of bednets and repellents, and chemoprophylaxis as the situation dictates.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

CURRENT OBSTACLES TO DEVELOPMENT

15

4 Current Obstacles to Development

THE SCIENCE Why is there still no effective malaria vaccine after decades of research and several development efforts? It may have been reasonable to expect failure in the early years of malaria research, given the lack of knowledge about the parasite and the pathogenesis of the disease and a limited understanding of immunology and immune function. Since then, however, both fundamental research and vaccine development efforts have greatly advanced our understanding of these issues. The limited success in malaria vaccine development reflects, in part, that needed answers of critical importance to product development efforts have neither been sought nor obtained in a systematic and coordinated way. Currently, for example, malaria vaccine research is being conducted on multiple fronts, employing different vaccine entities and research strategies. While such an approach has been extremely productive in expanding the fundamental knowledge base, it now appears that a more focused and coordinated strategy is needed for product selection and development. The scientific hurdles facing malaria vaccine developers are still imposing, however. There remains no known in vitro correlate of protection. The malaria parasite has multiple, immunologically distinct developmental stages and effective immune avoidance strategies. Single-antigen and single-stage vaccines have proved disappointing. Multi-antigen, multistage vaccines, which elicit different kinds of immune responses directed toward different antigens, appear more promising. High antibody levels can be effective against sporozoites and blood-stage parasites, but a cytotoxic cell response is needed to attack the critical liver stage, and antibodies are clearly needed to block transmission. Selecting the optimal antigens from among the stages in the parasite's life cycle and devising optimal formulations and delivery systems to elicit the desired immunologic response is a complex and difficult task, one that must be based on scientific knowledge, but will also require empirical testing of multiple potential vaccine products. Current knowledge of protective immunity to malaria has been derived, in part, from studies of malaria in animals and from human trials of experimental vaccines. Animal studies have great value for elucidating immune mechanisms and for developing concepts and new approaches. Experiments in rodents, however, have very limited value for predicting human immune response to specific antigens and individual formulations, and work with primates is expensive and constrained by the limited availability of animals. Success will ultimately depend on a combination of continued research in animals and an accelerated development effort emphasizing

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

CURRENT OBSTACLES TO DEVELOPMENT

16

early clinical trials of candidate vaccines in humans. Important information to be garnered includes the precise correlates of malarial immunity, the molecular basis for the duration of protection, and the necessary elements of the antigenic repertoire that must be included in an effective, multicomponent malaria vaccine. A substantial remaining problem in accelerating malaria vaccine research and development is the number of options that must be weighed and selected. Scores of parasite-derived proteins and parts of proteins have been identified, any of which may be important components of a useful vaccine. Several means for producing antigens, a number of new adjuvants, and new concepts such as nucleic acid vaccines and particle delivery systems must all be considered, and the most promising approaches tested, before substantial progress toward a new, effective malaria vaccine is ensured. COORDINATION There is currently no effective single locus of U.S. governmental activities directed toward malaria vaccine research and development. The Federal Malaria Vaccine Coordinating Committee (FMVCC) has attempted to fulfill this role, but lacks the authority and resources to do so (see Chapter 6 for a description of FMVCC). As a result, government-funded vaccine development remains disarticulated, with no overall strategy in place, and there is inadequate communication and coordination among malaria vaccine researchers and developers in government, academia, and industry. The consequences of this lack are profound. Representatives of industry at the workshop complained about the lack of a necessary “point of contact” in government that they could go to with questions or concerns relating to malaria vaccine product development. They noted that the lack of a federal strategy for vaccine development—one that necessarily focuses on a limited number of vaccine entities judged to have the highest probability of success—further discourages industry's involvement in malaria vaccine development. This lack of coordinated effort and strategic planning in the U.S. domestic arena extends to the international arena. As noted by the participants in the workshop, with the exception of FMVCC, there is no U.S. entity that effectively represents the views and concerns of the U.S. government, academia, and industry abroad.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR SCIENCE

17

5 Solutions for Science

As outlined in Chapter 3, “The Elements for Success Are Moving into Place,” the efforts of many investigators throughout the world have laid the foundation for the development of effective malaria vaccines. Recognizing that discoveries in basic science could render any current approaches obsolete and that there is no way to predict whether such discoveries will or will not occur, the following question needs to be answered before the next steps are identified: What is the most appropriate and efficient way to capitalize on previous work to achieve the objective of fielding effective malaria vaccines?

There was general consensus among workshop participants that the focus of the malaria vaccine effort during the next five years should be directed toward development of two separate vaccines with the following characteristics: • a vaccine that protects at least 90 percent of nonimmune visitors to malarious areas against the development of clinically manifest P. falciparum infection for 12 months or longer; • a vaccine that—when administered to children at 1, 2, and 9 months of age— reduces malaria-specific mortality in the first 6 years of life by 50 percent. It was agreed that the first vaccine would meet the needs of the private and military markets. The second vaccine would meet minimum efficacy levels for highly endemic regions of the developing world. A single vaccine could conceivably meet both requirements, but participants acknowledged that cost considerations, as well as immunologic and epidemiologic differences in vaccine requirements, justify setting two separate goals for vaccine development. A number of avenues need to be explored. For example, because Plasmodium is a complex, multistage microorganism, one premise holds that malaria vaccines will have to optimally induce both protective antibodies and CD4+ and CD8+ cytotoxic T-cell responses. Because we already have a validated system for testing preerythrocytic and sexual-stage vaccines in human volunteers by mosquito challenge, as well as defined protective immune

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR SCIENCE

18

mechanisms and antigens, malaria vaccine development can be used as a model for testing new vaccine technologies that should be of interest to industrial partners. Work with malaria vaccines has broadly advanced the field of vaccinology, although it has thus far failed to identify a successful vaccine against malaria itself. The first Escherichia coli–produced recombinant protein vaccine ever tested in humans was a malaria vaccine. The first synthetic peptide carrier conjugate vaccine tested in humans was also a malaria vaccine. The first assessment of DETOX (monophosphoryl lipid A and cell wall skeleton of mycobacteria) as an adjuvant for a vaccine against an infectious agent was made with malaria antigens. The first successful use of liposomes with monophosphoryl lipid A as a delivery system (adjuvant) in humans was in a malaria vaccine, and several new adjuvant formulations are now being tested in humans. The first multivalent recombinant vaccinia tested in humans was a malaria vaccine, and an early recombinant S. typhi vaccine tested in humans was a malaria vaccine. While no one can predict what a final successful malaria vaccine will be, workshop participants generally agreed that the elements for scientific success are moving into place. What is most needed now is a focused, systematic, and multisectoral approach to vaccine development that, as a first step, identifies the scientific hurdles remaining and the funds that will be required to overcome them. In the absence of an established, coordinated strategy, however, such assessments will have little validity and will understandably lack credibility.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR COORDINATION

19

6 Solutions for Coordination

Given the rapid resurgence of malaria, the multiplicity of candidate vaccines (over 40 at the time of this writing), and the multiple steps involved in the complex sequence of events necessary to translate fundamental research knowledge into a field-applicable, efficacious, and effective malaria vaccine, workshop participants felt it imperative that the process proceed with maximum efficiency, both with respect to time and to resource constraints. The following was therefore recommended: • A federal “Malaria Vaccine Development Board” should be established and given the responsibility, authority, and resources to carry out the strategy or strategies most likely to result in accelerated, successful development of malaria vaccines. The board should include representatives from academia, relevant federal government agencies, pharmaceutical and biotechnology companies, and foundations. A critical initial task of the board would be to identify a limited number of the most promising malaria vaccine candidates and to focus U.S. development efforts on these selections. The board should monitor progress in malaria vaccine development in both the public and private sectors; identify development needs, opportunities, and priorities and advise interested parties and funding agencies of these findings; provide financial and other support for high-priority development efforts; and encourage collaboration among academia and private and public sector entities. To succeed, the board must: 1. 2. 3. 4. 5.

have access to sufficient resources to fill gaps in the malaria vaccine development process in a timely manner; have a sustained, long-term commitment to malaria vaccine development; be able to access all phases of the malaria vaccine development process, through field implementation in immunization programs; have the flexibility to address rapidly changing needs, technologies, and priorities in the field of malaria vaccine development; be able to access, in a cost-effective manner, optimal technologies and development expertise, in either the private or public sector;

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR COORDINATION

6.

20

be able to provide the leadership in conducting U.S. malaria vaccine development efforts and in coordinating these with international academic researchers, corporations, and relevant organizations such as the World Health Organization, the World Bank, the United Nations Development Programme, and the Commission of the European Communities.

While there are historical precedents for aspects of the proposed Malaria Vaccine Development Board, none completely covers all of the facets described above. Some examples of precedents that may be examined for relevance to specific elements of the board's charge include the 1941 Commission on Influenza of the Armed Forces Epidemiology Board, the National Task Force on AIDS Drug Development, and the National Foundation for Infantile Paralysis. The board's development strategy should incorporate the action steps required for accelerated, cost-effective production, evaluation, and field application of the two malaria vaccines. The estimated costs of such a program and the optimal mix of governmental, academic, industrial, and foundation participation and support required should also be determined. In these determinations the board must clearly document the scientific foundation for any recommendations. In addition, because a major incentive for industrial investment in vaccine development is the size of the potential market for the vaccine, it is recommended that the board immediately commission independent market analyses for each of the proposed vaccine types, and that this information be made widely available to the global vaccine industry. As a first step, it is recommended that the board consider convening a meeting of members to develop an agreement to ensure access to reagents in both the public and the private sector that could be useful in developing and conducting assays required to assess vaccine candidates in animals and humans. Such reagents should include, but not be limited to, purified recombinant proteins, synthetic peptides, live recombinant viruses and bacteria, DNA plasmids, and monoclonal antibodies. Having established strategies for sharing reagents equitably and consistently, the board could then address the more difficult goal of establishing productive, consensual alliances among government, academia, the nongovernmental sector, and industry for the purpose of rapid malaria vaccine development. PREREQUISITES FOR SUCCESS In order for the proposed Malaria Vaccine Development Board to be successful, effective leadership is necessary, and each participating entity must agree on the accepted strategy for vaccine development. This requires that each party identify areas of interest within the overall process, as well as areas of comparative advantage. Each entity should have a vested interest in sharing information and resources, and must find an economical method of doing so.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR COORDINATION

21

MODELS FOR COORDINATION AND LEADERSHIP There is ample precedent for coordination of vaccine research and development. Commissions established by military medical boards have successfully addressed similar problems with other diseases. The first polio vaccines were developed largely under the auspices of the National Foundation for Infantile Paralysis, which coordinated all aspects of the process, from initial production to clinical evaluation. A Polio Vaccine Committee, comprised of scientists, physicians, and other experts, provided ongoing commitment and advice, while the National Foundation provided necessary funding. Strong leadership was a major component of the success of the commissions and the National Foundation. Another precedent for coordination is the National Task Force on AIDS Drug Development, which was chartered from 1993 to 1995 to identify and remove obstacles to AIDS drug discovery and development efforts. The task force consisted of 15 members from academia, industry, and community constituency groups; the directors of the National Institutes of Health and Federal Drug Administration; and the assistant secretary for health, who acted as chair. The task force forwarded a series of recommendations to the secretary for health, DHHS, that focused on incentives for increased involvement of industry and academia in AIDS drug discovery and development efforts. An important question is whether these models are useful paradigms for the malaria vaccine effort. By and large, past efforts represent attempts to deal with product development issues. In many of these cases, the issues were sufficiently defined, and a straightforward, but detailed, development plan could be developed and implemented. In the case of malaria vaccine development, however, there are multiple candidate vaccines, multiple production technologies, and many other complex issues that need to be considered. Thus, as will be discussed below, coordination of malaria vaccine R&D requires not only a perspective on product development, but also on the management of complex, multiorganizational endeavors. IMPLEMENTING COORDINATION Initial Considerations Factors limiting coordination and collaboration derive from several sources. First, different agencies or groups have distinct missions. For example, the primary objective of the Department of Defense malaria vaccine development program is to develop vaccines that will protect U.S. military personnel deployed in endemic areas. In contrast, the primary objective of the Malaria Vaccine Development Program of the U.S. Agency for International Development (USAID) is to develop vaccines for populations permanently residing in endemic areas. Because these end objectives differ substantially

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR COORDINATION

22

from one another, it is possible that the agencies may elect to develop different types of vaccines, thereby limiting the perceived need to cooperate. In this hypothetical instance, it is still possible that the number of shared steps in the development process for each vaccine candidate will provide sufficient impetus for the sharing of resources. A second hindrance to coordination stems from insufficient internal resources. A paucity of funding for a given agency program will limit the ability of that agency to collaborate with other agencies in a useful manner without crippling its own program. Finally, there are bureaucratic and institutional hurdles. For example, coordination requires that participants respond to requests for assistance in a timely manner. Regardless of the cause, failure to do so delays the development process and leads other participants to seek alternative, and perhaps less productive, partnerships or to go it alone. In contrast, specific expertise and resources may be vested in individual agencies, so that coordination and collaboration among these agencies can be seen as synergistic for the development process as a whole. For example, the Centers for Disease Control and Prevention (CDC) has a specific mandate and expertise in the epidemiology and field studies of malaria, while the National Institutes of Health (NIH) vigorously supports laboratory and clinical studies of malaria. In such instances, it is important that the individual agencies coordinate their efforts, capabilities, and resources within the larger context of vaccine R&D. Prioritization, Product Development, and Process Management At the simplest level, coordinated malaria vaccine R&D requires participants to distinguish more promising malaria vaccine candidates from those with less promise, and to guide the most promising candidates through the development process. There is thus a need to prioritize candidate vaccines based on desirable characteristics, as well as to judge the probability of successful development. The desirable characteristics should reflect not only scientific and public health considerations, but also technical considerations related to feasibility; economic concerns; and, ultimately, delivery. The establishment of priorities and criteria is also important for determining go/no-go criteria for product development. Early identification of such criteria would permit investigators and agencies working on lower-priority candidates to know what technical issues need to be addressed in order to improve the standing of their candidates. Procedures for the systematic setting of priorities and product development of the kind described above are well established in both the public and private sectors. They presuppose, however, relatively well-defined candidate vaccines, preferably few in number, so that the decision points in the development process are minimized and fall within a relatively short time frame.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

SOLUTIONS FOR COORDINATION

23

Initial Efforts to Coordinate Malaria Vaccine R&D Beginning in the mid-1980s a number of federal agencies recognized that malaria vaccine R&D was proceeding, often in a disjointed fashion, in a variety of agencies, and that sharing of information could be mutually beneficial. The number of interactions subsequently increased until the late 1980s, when they were formalized through the formation of an ad hoc group, the Federal Malaria Vaccine Coordinating Committee (FMVCC), which met on a regular basis under the auspices of the USAID Malaria Vaccine Development Program. In 1995 the venue for FMVCC was changed to the NIH. By consensus, participants began to focus on more proactive efforts to accelerate malaria vaccine R&D through increased collaboration and cooperation among the participants. Several task forces charged with development of selected malaria vaccine products were established and have begun to coordinate the steps in the development process. In addition, FMVCC began to exchange information, identify generic gaps in the development process, establish collaborations to evaluate new vaccine technologies, and consider how vaccines might be evaluated in clinical and field settings. It also recognized the important need to reach out to other entities in the private sector and the international community. FMVCC was crucial in beginning the transition from coordinating individual product development efforts to the more complex task of process management. This process should continue. THE NEXT STEPS While acknowledging the accomplishments of FMVCC, workshop participants recognized that an additional major step must be taken. Coordination of research and communication between managers of development programs is essential, but not sufficient to meet the challenge of malaria vaccine development. Workshop members agreed that a powerful and authoritative federal Malaria Vaccine Development Board is needed to forge the alliance among government agencies and to establish the necessary partnerships with both the academic community and the vaccine industry.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

REFERENCES

24

References

Alonso, P., T. Smith, J. R. M. A. Schellenberg, et al. 1994. Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet 344: 1175–1181. Alonso, P. L., S. W. Lindsay, J. R. Armstrong, M. Conteh, A. G. Hill, P. H. David, G. Fegan, A. de Francisco, A. J. Hall, F. C. Shenton, et al., 1991. The effect of insecticide-treated bed nets on mortality of Gambian children. Lancet 337: 1499–1502. Beach, R. F., T. K. Ruebush 2nd, J. D. Sexton, P. L. Bright, A. W. Hightower, J. G. Breman, D. L. Mount, and A. J. Oloo. 1993. Effectiveness of permethrin-impregnated bed nets and curtains for malaria control in a holoendemic area of western Kenya. Am. J. Trop. Med. Hyg. 49: 290–300. Binka, F. N., A. Kubaje, M. Adjulik, L. A. Williams, C. Lengeler, G. H. Maude, G. E. Armah, D. Kajhara, J. H. Adlamah, and P. G. Smith. 1996. Impact of permethrin-impregnated bednets on child mortality in Kassena-Kankana district, Ghana: a randomized controlled trial. Trop. Med. Intl. Hlth. 1: 147–154. Brewer, T. G., J. O. Peggins, S. J. Grate, J. M. Petras, B. S. Levine, P. J. Weina, J. Swearengen, M. H. Heiffer, and B. G. Schuster. 1994. Neurotoxicity in animals due to arteether and artemether. Trans. R. Soc. Trop. Med. Hyg. 88 (Suppl. 1):S33–S36. Carme, B., J. C. Bouquety, and H. Plassart. 1993. Mortality and sequelae due to cerebral malaria in African children in Brazzaville, Congo. Am. J. Trop. Med. Hyg. 48: 216–221. Curtis, C. F. 1996. Impregnated bednets, malaria control and child mortality in Africa. Trop. Med. Intl. Hlth. 1: 137–138. D'Alessandro, U., A. Leach, C. J. Drakeley, et al., 1995, Efficacy trial of malaria vaccine SPf66 in Gambian infants. Lancet 346: 462–267. Doumbo, O., S. F. Traoré, Y. Sow, M. Dembele, G. Soula, A. Coulibaly, A. Dolo, O. Sangare, O. Koita, E. Pichard, et al., 1991. Impact of curtains and blankets impregnated with permethrin on the malarial indicators and the number of malarial attacks per child in a village in an area hyperendemic for malaria on the Malian savannah. Bull. Soc. Pathol. Exot. 84: 761–774. Hoffman, S. L., ed. 1996. Malaria Vaccine Development: A Multi-Immune Response Approach. Washington, D.C.: American Society of Microbiology.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

REFERENCES

25

Hviid, L., and P. H. Jakobsen, eds. 1995. Proceedings of the First African Malaria Vaccine Testing Network Meeting. Arusha, Tanzania, 22–24 February 1995. Copenhagen: University of Copenhagen. Isaacson, M. 1989. Airport malaria: a review. Bull. WHO 87: 737–743. Lederberg, J., R. E. Shope, and S. Oaks. 1992. Emerging Infections: Microbial Threats to Health in the United States. Washington, D.C.: National Academy Press. Lobel, H. O., M. Miani, T. Eng, K. W. Bernard, A. W. Hightower, and C. C. Campbell. 1993. Longterm malaria prophylaxis with weekly mefloquine. Lancet 341: 848–851. Luby, J. P., M. G. Schultz, T. Nowosiwsky, and R. L. Kaiser. 1967. Introduced malaria at Fort Benning, Georgia, 1964–1965. Am. J. Trop. Med. Hyg. 16: 146–153. Maldonado, Y. A., B. L. Nahlen, R. R. Roberto, M. Ginsberg, E. Orellana, M. Mizrahi, K. McBarron, H. O. Lobel, and C. C. Campbell. 1990. Transmission of Plasmodium vivax in San Diego, County, California, 1986. Am. J. Trop. Med. Hyg. 42: 3–9. Marsh, K. 1992. Malaria—a neglected disease? Parasitology 104:S53–S69. Mbogo, C. N., R. W. Snow, C. P. Khamala, E. W. Kabiru, J. H. Ouma, J. I. Githure, K. Marsh, and J. C. Beier. 1995. Relationship between Plasmodium falciparum transmission by vector populations and the incidence of severe disease at nine sites on the Kenyan coast. Am. J. Trop. Med. Hyg. 52: 201–206. Miller, L. H., M. F. Good, and G. Milon. 1994. Malaria pathogenesis. Science264:1878–1883 . Neel, S. 1973. Vietnam Studies: Medical Support, 1965–1970. Washington, D.C.: U.S. Department of the Army. Nevill, C. G., E. S. Some, V. O. Mungala, W. Mutemi, L. New, K. Marsh, C. Lengeler, and R. W. Snow. 1996. Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Trop. Med. Intl. Hlth. 1:139–146. Nussenzweig, R. S., J. P. Vanderberg, H. Most, and C. Orton. 1967. Protective immunity produced by the injection of X-irradiated sporozoites of Plasmodium berghei. Nature 216: 160–162. Oakes, S., et al. 1991. Malaria: Obstacles and Opportunities. Washington, D.C.: National Academy Press. Trang, T. T. M., N. H. Phu, H. Vinh, T. T. Hien, B. M. Cuong, T. T. H. Chau, N. T. H. Mai, D. J. Waller, and N. J. White. 1992. Acute renal failure in patients with severe falciparum malaria. Clin. Infect. Dis. 15: 874–880. Warrell, D. A., M. E. Molyneux, and P. F. Beales , eds. 1990. Severe and complicated malaria . Trans. R. Soc. Trop. Med. Hyg. 84 (Suppl. 2): 1–65. Weber, M. M., K. Böker, R. D. Horstmann, and J. H. H. Ehrich. 1991. Renal failure is a common complication in non-immune Europeans with Plasmodium falciparum malaria. Trop. Med. Parasitol. 42: 115–118.

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. REFERENCES

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

26

Wernsdorfer, W. H. 1994. Epidemiology of drug resistance. Acta Tropica 56: 143–156. WHO (World Health Organization). 1996. World Health Organization Fact Sheet N94 (revised). 1996. Malaria. Geneva: World Health Organization .

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

APPENDIX

27

Appendix Workshop Agenda

INSTITUTE OF MEDICINE National Academy of Sciences Board on International Health Board on Health Promotion and Disease Prevention Workshop on Malaria Vaccines 19–20 October 1995 Cecil and Ida Green Building, Room 104 2001 Wisconsin Avenue, N.W. Washington, DC 20007 (202) 334-3904 AGENDA 19 October 1995 8:30 a.m.–8:45 a.m.

Welcome and Introductions Philip Russell, Chair, IOM Committee on Malaria Vaccines

8:45 a.m.–10:45 a.m.

SESSION I: SETTING THE STAGE

(8:45 a.m.–9:15 a.m.)

Malaria: The Deteriorating Situation Donald Krogstad, Tulane University School of Public Health and Tropical Medicine, USA

(9:15 a.m.–9:45 a.m.)

The Promise of Malaria Vaccines Jerald Sadoff, Merck Research Laboratories, USA

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

APPENDIX

(9:45 a.m.–10:05 a.m.)

28

Malaria Vaccines in the Field: A Perspective from the Africa Malaria Vaccine Testing Network Wenceslaus Kilama, The African Malaria Vaccine Testing Network, Tanzania

(10:05 a.m.–10:30 a.m.)

Discussion Moderator: Philip Russell

10:30 a.m.–11:00 a.m.

Break

11:00 a.m.–12:00 p.m.

SESSION II: MALARIA AS A PARADIGM Stephen Hoffman, Naval Medical Research Institute, USA

(11:40 a.m.–12:00 p.m.)

Discussion Moderator: Louis Miller, National Institutes of Health, USA

12:00 p.m.–1:00 p.m.

Lunch

1:00 p.m.–3:30 p.m.

SESSION III: CURRENT APPROACHES TO MALARIA VACCINE DEVELOPMENT

(1:00 p.m.–1:25 p.m.)

Preerythrocytic Vaccines Ruth Nussenzweig, New York University Medical Center, USA

(5 min.)

Questions

(1:30 p.m.–1:55 p.m.)

Erythrocytic Vaccines Graham Brown, The Walter and Eliza Hall Institute of Medical Research, Australia

(5 min.)

Questions

(2:00 p.m.–2:25 p.m.)

Transmission Blocking Vaccines David Kaslow, National Institutes of Health, USA

(5 min.)

Questions

(2:30 p.m.–3:30 p.m.)

Discussion: Potential Immunologic Obstacles toDevelopment of an Optimal Multi-Immune Response, Multi-Stage Malaria Vaccine Moderator: W. R. Ballou, Walter Reed Army Institute of Research, USA

3:30 p.m.–4:00 p.m.

Break

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

APPENDIX

4:00 p.m.–5:30 p.m.

29

SESSION IV: ROUNDTABLE ON U.S. FEDERAL MALARIA VACCINE ACTIVITIES

Summary of Agency Activities 20 October 1995 (4:00 p.m.–4:15 p.m.)

Public Health Service Daniel Colley, Centers for Disease Control and Prevention

(4:15 p.m.–4:30 p.m.)

Department of Defense William Bancroft, U.S. Army Medical Research and Materiel Command

(4:30 p.m.–4:45 p.m.)

U.S. Agency for International Development Carter Diggs, USAID

(4:45 p.m.–5:00 p.m.)

Federal Malaria Vaccine Coordinating Committee Lee Hall, National Institutes of Health

(5:00 p.m.–5:30 p.m.)

Roundtable Discussion Moderator: Lee Hall

5:30 p.m.

Reception (North Prefunction Area, directly outside meeting room)

8:30 a.m.–10:15 a.m.

SESSION V: ROUNDTABLE ON INDUSTRIAL SECTOR ACTIVITIES

(8:30 a.m.–9:00 a.m.)

Malaria Vaccine Development: A Perspective from Industry Russell Howard, Glaxo-Wellcome

(9:00 a.m.–9:35 a.m.)

The following participants may wish to present for 5 min. each: Ian Bathurst, LXR Biotechnology W. Neal Burnette, Molecular Pharmaceutics Corporation Kenneth Guito, Connaught Laboratories Maurice Hilleman, The Merck Institute Adeoye Olukotun, Bristol-Myers Squibb Company John Tine, Virogenetics Corporation

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,

Copyright © 1996. National Academies Press. All rights reserved.

About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution.

APPENDIX

(9:35 a.m.–10:15 a.m.)

30

Roundtable Discussion Moderator: Russell Howard

10:15 a.m.–10:45 a.m.

Break

10:45 a.m.–12:15 a.m.

SESSION VI: ROUNDTABLE ON INTERNATIONAL COLLABORATION

(10:45 a.m.–11:00 a.m.)

Overview of Global Malaria Vaccine Activities Howard Engers, WHO Special Programme for Research and Training in Tropical Diseases, Switzerland

(11:00 a.m.–11:15 a.m.)

DANIDA and Commission of European Communities Palle Jakobsen, Denmark

(11:15 a.m.–11:25 a.m.)

African Malaria Vaccine Testing Network Wenceslaus Kilama, Tanzania

(11:25 a.m.–11:35 a.m.)

Walter and Eliza Hall Institute of Medical Research Graham Brown, Australia

(11:35 a.m.–11:45 a.m.)

Medical Research Council Michael Davies, Great Britain

(11:45 a.m.–12:15 p.m.)

Roundtable Discussion Moderator: Howard Engers (session will include participants from the Roundtable on U.S. Federal Malaria Vaccine Activities)

12:15 p.m.–1:00 p.m.

SESSION VII: SUMMARY AND DISCUSSION OF FINDINGS, CONCLUSIONS, AND RECOMMENDATIONS Philip Russell, IOM Committee Chair

1:00 p.m.

Workshop Adjournment

1:30 p.m.–5:00 p.m.

EXECUTIVE SESSION Workshop Committee on Malaria Vaccines

Vaccines Against Malaria, National Academies Press, 1996. ProQuest Ebook Central,