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BIBTEX RIS

Ad35.CS.01 - RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults

2015; Public Library of Science; Volume: 10; Issue: 7 Linguagem: Inglês

10.1371/journal.pone.0131571

ISSN

1932-6203

Autores

Christian F. Ockenhouse, Jason A. Regules, Donna Tosh, Jessica Cowden, April K. Kathcart, James F. Cummings, Kristopher Paolino, James E. Moon, Jack Komisar, Edwin Kamau, Thomas Oliver, Austin Chhoeu, Jitta Murphy, Kirsten E. Lyke, Matthew B. Laurens, Ashley J. Birkett, Cynthia Lee, Rich Weltzin, Ulrike Wille-Reece, Martha Sedegah, Jenny Hendriks, Isabella Versteege, Maria Grazia Pau, Jerold Sadoff, Yannick Vanloubbeeck, Marc Lievens, Dirk Heerwegh, Philippe Moris, Yolanda Guerra Mendoza, Erik Jongert, Joe Cohen, Gérald Voss, W. Ripley Ballou, Johan Vekemans,

Tópico(s)

vaccines and immunoinformatics approaches

Resumo

Methods In an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR-group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection. Results ARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-γ enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001). Conclusions An increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime-boost regimens and/or additional target antigens. Trial Registration ClinicalTrials.gov NCT01366534

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