Details

Autor(en) / Beteiligte

• 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, D. Gray

Titel

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

Ist Teil von

• The Journal of infectious diseases, 2009-08, Vol.200 (3), p.337-346

Ort / Verlag

Oxford: The University of Chicago Press

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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 deter-mine 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. Trial registration ClinicalTrials.gov identifier NCT00075049.