Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research.
The goal of the Malaria Vaccine Program at the Walter Reed Army Institute of Research (WRAIR) is to develop a licensed multi-antigen, multi-stage vaccine against Plasmodium falciparum able to prevent all symptomatic manifestations of malaria by preventing parasitemia. A secondary goal is to limit disease in vaccinees that do develop malaria. Malaria prevention will be achieved by inducing humoral and cellular immunity against the pre-erythrocytic circumsporozoite protein (CSP) and the liver stage antigen-1 (LSA-1). The strategy to limit disease will target immune responses against one or more blood stage antigens, merozoite surface protein-1 (MSP-1) and apical merozoite antigen-1 (AMA-1). The induction of T- and B-cell memory to achieve a sustained vaccine response may additionally require immunization with an adenovirus vector such as adenovirus serotype 35. RTS,S, a CSP-derived antigen developed by GlaxoSmithKline Biologicals in collaboration with the Walter Reed Army Institute of Research over the past 17 years, is the cornerstone of our program. RTS,S formulated in AS02A (a GSK proprietary formulation) is the only vaccine candidate shown in field trials to prevent malaria and, in one instance, to limit disease severity. Our vaccine development plan requires proof of an individual antigen's efficacy in a Phase 2 laboratory challenge or field trial prior to its integration into an RTS,S-based, multi-antigen vaccine. Progress has been accelerated through extensive partnerships with industrial, academic, governmental, and non-governmental organizations. Recent safety, immunogenicity, and efficacy trials in the US and Africa are presented, as well as plans for the development of a multi-antigen vaccine.
Heppner
D Gray
DG
Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. donald.heppner@na.amedd.army.mil
Kester
Kent E
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Ockenhouse
Christian F
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Tornieporth
Nadia
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Ofori
Opokua
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Lyon
Jeffrey A
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Stewart
V Ann
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Dubois
Patrice
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Lanar
David E
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Krzych
Urszula
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Moris
Philippe
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Angov
Evelina
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Cummings
James F
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Leach
Amanda
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Hall
B Ted
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Dutta
Sheetij
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Schwenk
Robert
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Hillier
Collette
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Barbosa
Arnoldo
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Ware
Lisa A
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Nair
Lalitha
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Christian A
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Withers
Mark R
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Ogutu
Bernhards
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Polhemus
Mark E
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Fukuda
Mark
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Pichyangkul
Sathit
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Gettyacamin
Montip
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Diggs
Carter
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Soisson
Lorraine
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Milman
Jessica
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Dubois
Marie-Claude
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Garçon
Nathalie
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Tucker
Kathryn
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Wittes
Janet
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Plowe
Christopher V
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Mahamadou A
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Ogobara K
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Pau
Maria G
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Goudsmit
Jaap
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Ballou
W Ripley
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Cohen
Joe
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D000047:Academies and Institutes; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D002986:Clinical Trials as Topic; D005822:Genetic Vectors; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000517:prevention & control; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D014481:United States
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C493155:RTS,S-AS02A vaccine; C090077:apical membrane antigen I, Plasmodium; C067302:liver stage-specific antigen, Plasmodium