Towards an RTS,S-Based, Multi-Stage, Multi-Antigen Vaccine Against Falciparum Malaria: Progress at the Walter Reed Army Institute of Research

Authors

• D. Gray Heppner Jr., Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Kent E. Kester, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Christian F. Ockenhouse, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Nadia Tornieporth, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• Opokua Ofori, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• Jeffrey A. Lyon, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• V. Ann Stewart, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Patrice Dubois, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• David E. Lanar, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Urszula Krzych, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Philippe Moris, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• Evelina Angov, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• James F. Cummings, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Amanda Leach, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• B. Ted Hall, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Sheetij Dutta, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Robert Schwenk, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Collette Hillier, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Arnoldo Barbosa, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Lisa A. Ware, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Lalitha Nair, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Christian A. Darko, Walter Reed Army Institute of Research, Department of Immunology, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
• Mark R. Withers, United States Army Medical Research Unit-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
• Bernhards Ogutu, United States Army Medical Research Unit-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
• Mark E. Polhemus, United States Army Medical Research Unit-Kenya, Kenya Medical Research Institute, Nairobi, Kenya
• Mark Fukuda, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand
• Sathit Pichyangkul, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand
• Montip Gettyacamin, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand
• Carter Diggs, United States Agency for International Development, Washington, DC, USA
• Lorraine Soisson, United States Agency for International Development, Washington, DC, USA
• Jessica Milman, PATH’s Malaria Vaccine Initiative, Bethesda, MD, USA
• Marie-Claude Dubois, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• Nathalie Garcon, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• Kathryn Tucker, Statistics Collaborative Incorporated, Washington, DC, USA
• Janet Wittes, Statistics Collaborative Incorporated, Washington, DC, USA
• Christopher V. Plowe, Center for Vaccine Development, University of Maryland, Baltimore, MD, USA
• Mahamadou A. Thera, Malaria Research and Training Center, University of Bamako, Bamako, Mali
• Ogobara K. Duombo, Malaria Research and Training Center, University of Bamako, Bamako, Mali
• Maria G. Pau, Crucell Holland, B.V., Leiden, The Netherlands
• Jaap Goudsmit, Crucell Holland, B.V., Leiden, The Netherlands
• W. Ripley Ballou, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium
• Joe Cohen, GlaxoSmithKline Biologicals, s.a., Rixensart, Belgium

Document Type

Article

Date of this Version

2005

Comments

Published in Vaccine 23 (2005) 2243–2250.

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.