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- Title
Randomized, Double-Blind, Phase 2a Trial of Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria-Naive Adults: Safety, Efficacy, and Immunologic Associates of Protection.
- Authors
Kester, Kent E.; Cummings, James F.; Ofori-Anyinam, Opokua; Ockenhouse, Christian F.; Krzych, Urszula; Moris, Philippe; Schwenk, Robert; Nielsen, Robin A.; Debebe, Zufan; Pinelis, Evgeny; Juompan, Laure; Williams, Jack; Dowler, Megan; Stewart, V. Ann; Wirtz, Robert A.; Dubois, Marie-Claude; Lievens, Marc; Cohen, Joe; Ballou, W. Ripley; Heppner, Jr., D. Gray
- Abstract
Background. To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS,S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals). Methods. In a double-blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/ AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later. Results. RTS,S/AS01B and RTS,S/AS02A were well tolerated and were safe. The efficacy of RTS,S/AS01B and RTS,S/AS02A was 50% (95% confidence interval [CI], 32.9%-67.1%) and 32% (95% CI, 17.6%-47.6%), respectively. At the time of initial challenge, the RTS,S/AS01B group had greater circumsporozoite protein (CSP)-specific immune responses, including higher immunoglobulin (Ig) G titers, higher numbers of CSP-specific CD4+ T cells expressing ⩾2 activation markers (interleukin-2, interferon [IFN]-γ, tumor necrosis factor-α, or CD40L), and more ex vivo IFN-γ enzyme-linked immunospots (ELISPOTs) than did the RTS,S/AS02A group. Protected vaccine recipients had a higher CSP-specific IgG titer (geometric mean titer, 188 vs 73 μg/mL; P < .001), higher numbers of CSP-specific CD4+ T cells per 106 CD4+ T cells (median, 963 vs 308 CSP-specific CD4+ T cells/106 CD4+ T cells; P < .001), and higher numbers of ex vivo IFN-γ ELISPOTs (mean, 212 vs 96 spots/million cells; P < .001). At rechallenge, 4 of 9 vaccine recipients in each group were still completely protected. Conclusions. The RTS,S/AS01B malaria vaccine warrants comparative field trials with RTS,S/AS02A to determine the best formulation for the protection of children and infants. The association between complete protection and immune responses is a potential tool for further optimization of protection.
- Subjects
GLAXOSMITHKLINE Biologicals SA; IMMUNIZATION of children; PREVENTIVE medicine; MALARIA vaccines; VACCINATION; MALARIA
- Publication
Journal of Infectious Diseases, 2009, Vol 200, Issue 3, p337
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1086/600120