Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research.

Abstract

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.

• Authors: D Gray Heppner Jr, Kent E Kester, Christian F Ockenhouse, Nadia Tornieporth, Opokua Ofori, Jeffrey A Lyon, V Ann Stewart, Patrice Dubois, David E Lanar, Urszula Krzych, Philippe Moris, Evelina Angov, James F Cummings, Amanda Leach, B Ted Hall, Sheetij Dutta, Robert Schwenk, Collette Hillier, Arnoldo Barbosa, Lisa A Ware, Lalitha Nair, Christian A Darko, Mark R Withers, Bernhards Ogutu, Mark E Polhemus, Mark Fukuda, Sathit Pichyangkul, Montip Gettyacamin, Carter Diggs, Lorraine Soisson, Jessica Milman, Marie-Claude Dubois, Nathalie Garçon, Kathryn Tucker, Janet Wittes, Christopher V Plowe, Mahamadou A Thera, Ogobara K Duombo, Maria G Pau, Jaap Goudsmit, W Ripley Ballou, Joe Cohen
• Journal: Vaccine (Vaccine) Vol. 23 Issue 17-18 Pg. 2243-50 (Mar 18 2005) ISSN: 0264-410X [Print] Netherlands
• PMID: 15755604 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Antigens, Protozoan
• Malaria Vaccines
• Membrane Proteins
• Merozoite Surface Protein 1
• Protozoan Proteins
• RTS,S-AS02A vaccine
• apical membrane antigen I, Plasmodium
• liver stage-specific antigen, Plasmodium

Topics

• Academies and Institutes
• Adenoviridae (genetics)
• Animals
• Antigens, Protozoan (genetics, immunology, isolation & purification)
• Clinical Trials as Topic
• Genetic Vectors
• Humans
• Malaria Vaccines (genetics, immunology, isolation & purification, pharmacology)
• Malaria, Falciparum (prevention & control)
• Membrane Proteins (genetics, immunology)
• Merozoite Surface Protein 1 (genetics, immunology)
• Plasmodium falciparum (genetics, immunology)
• Protozoan Proteins (genetics, immunology)
• United States