07/08/05

Glassman Lecture

Parallel Paths in the Quest for a Malaria Vaccine: Use of Modern Vaccinology and Genomics vs. Basic Parasitology and Entomology to Realize the Goal
Stephen L. Hoffman, Sanaria Inc.

Introduction by Stephen L. Hajduk, Marine Biological Laboratory


Lecture Abstract:
Scientists have been working for more than 25 years to develop malaria vaccines. Modern, recombinant, subunit malaria vaccine development depends in large part on characterizing mechanisms of protective immunity and the antigen targets of these protective immune responses, and developing vaccine delivery systems that induce the required immune responses against the identified targets. The genomic sequences of Plasmodium falciparum, P. yoelii, and Homo sapiens have provided a wealth of information upon which to build experiments designed to characterize immune mechanisms and antigen targets, and optimize vaccine delivery systems. Translating this information into highly effective, sustainable malaria vaccines will be a difficult, expensive, long process.

In fact only one P. falciparum protein, which was discovered and shown to be protective using modern scientific methods, the circumsporozoite protein (PfCSP), has been shown to reproducibly elicit immune responses that prevent infection in humans. Clinical development of PfCSP vaccines has been in progress for 20 years. The best experimental recombinant protein vaccine is based entirely on the PfCSP delivered in a strong adjuvant and is called RTS,S/AS02A. This vaccine protects 40%-45% of experimentally challenged volunteers against P. falciparum infection for 2-3 weeks. Recently it was shown in 1-4 year olds in an area of Mozambique with modest transmission intensity of P. falciparum to reduce the numbers of first clinical episodes of P. falciparum malaria by 22.6% and the numbers of re-infections with P. falciparum by 10.4% during 6 months of follow up. Despite this relatively poor performance against all clinical episodes of malaria and against infection, it reduced the numbers of cases of severe disease by 57%. For this reason there is now great enthusiasm for testing this vaccine in the infants who will have to be the recipients of the vaccine in any program of vaccination. Because of the importance of malaria vaccine development, in parallel there are over 70 other approaches to subunit, modern, recombinant malaria vaccine development in progress.

At Sanaria we are working on a completely different approach to malaria vaccine development. The goal is to develop a practically manufactured and administered, safe, non-toxic, effective, non-replicating, metabolically active whole parasite P. falciparum sporozoite vaccine. This approach is based on the fact that when the immunogens, radiation attenuated P. falciparum sporozoites, are administered via the bites of infected mosquitoes, they elicit immune responses that completely protect greater than 90% of recipients against experimental P. falciparum challenge for at least 10 months. Current status of these and other approaches to develop vaccines to reduce the 2,700 to 8,100 daily deaths in infants and children in Africa will be discussed.


Stephen L. Hoffman, MD, DTMH is the founder and Chief Executive and Scientific Officer of Sanaria Inc., and co-founder and Chairman of Protein Potential LLC, vaccine development companies in Rockville, Maryland. He was Senior Vice President of Biologics at Celera Genomics in Rockville from December 2000 through July 2002, where he led the effort to use genomic and proteomic information to develop immunotherapeutic and other biologics products, and coordinated the Anopheles gambiae genome sequencing effort. Dr. Hoffman retired in early 2001 as a Captain in the Medical Corps of the U.S. Navy, where he was the Director of the Malaria Program, Naval Medical Research Center (NMRC) in Bethesda, Maryland, and Coordinator of the Department of Defense’s Malaria Vaccine Development Efforts. He initiated the Department of Defense’s Plasmodium genome sequencing effort in 1995. He serves as Adjunct Professor of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences in Bethesda, and Visiting Professor of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Dr. Hoffman received his B.A. from the University of Pennsylvania, his M.D. from Cornell University, and a Diploma of Tropical Medicine and Hygiene (DTMH) from the London School of Hygiene and Tropical Medicine. Dr. Hoffman was a resident and chief resident in Family Medicine at the University of California San Diego (UCSD) from 1975 to 1978, and on the faculty at UCSD and co-founder and director of the Tropical Medicine and Travelers Clinic there from 1979 to 1980. He was on active duty in the U.S. Navy from 1980 through 2001, first serving as the Head of the Department of Clinical Investigation and Epidemiology at NAMRU-2 in Jakarta, Indonesia, where he worked from 1980 to 1984 on typhoid fever, malaria, lymphatic dwelling filariasis, cholera, and dengue. In 1985 he joined the malaria vaccine development program at NMRC and at the Walter Reed Army Institute of Research (WRAIR), and in 1987 became director of the NMRC Malaria Program. He was an attending physician in the Division of Infectious Diseases at the National Naval Medical Center from 1990 to 2001. Dr. Hoffman has had extensive field experience in Southeast Asia, Africa, and South America. He has received numerous awards, including the Bailey K. Ashford Medal from the American Society of Tropical Medicine and Hygiene in 1992, the Legion of Merit from the U.S. Navy, in 1993 and 2000, the COL George W. Hunter III Certificate in 1994, and the Captain Robert Dexter Conrad Award, the U.S. Navy’s most prestigious award for scientific achievement by anyone in any field, regardless of military affiliation, in 1998. He is a member of the American Society for Clinical Investigation, the Association of American Physicians, and the Institute of Medicine of the National Academies. Dr. Hoffmann was President of the American Committee on Clinical Tropical Medicine and Traveler’s Health from 1996 to 1998, a Councilor of the American Society of Tropical Medicine and Hygiene (ASTMH) from 1990 to 1993, and President of the ASTMH from 2000 to 2001. He served on World Health Organization steering and advisory committees since 1993, and serves on multiple advisory and editorial boards. Dr. Hoffman holds seven patents and has more than 20 pending; has edited two books on malaria vaccine development, is founding Co-editor in Chief of Tropical Medicine: Science and Practice, and has more than 340 scientific publications.

Stephen L. Hajduk is a Senior Scientist at the Marine Biological Laboratory (MBL) in the Josephine Bay Paul Center, the Director of the MBL's Global Infectious Diseases Program and Professor of Molecular Microbiology and Immunology at Brown University.  Dr. Hajduk received his B.S. from the University of Georgia and his Ph.D. in Biology from the University of Glasgow, UK.  He was a visiting scholar at the University of Amsterdam and a postdoctoral fellow at Johns Hopkins University before joining the Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham (UAB). Dr. Hajduk was promoted to full-professor in 1991 and was named founding director of the Center for Community Outreach Development in 1998.

Dr. Hajduk's research on African sleeping sickness has been featured in Science, Nature, and Cell and reported in BBC News, BBC International News, and Associated Press Service.  He has served on Scientific Review Boards for the Howard Hughes Medical Institute (HHMI), the National Institutes of Allergies and Infectious Disease (NIAID), the National Research Council, the Wellcome Trust (UK) and the Burroughs Wellcome Fund Advisory Board for Molecular Pathogenesis.  

About the Glassman Lecture:
The Glassman Lecture is held in honor of the late Harold N. Glassman who left a generous bequest to the MBL which resulted in the establishment of the Harold N. Glassman fund, the income from which is used to support an annual Friday Evening Lecture on an important topic in biological research.