1. Ad35.CS.01 - RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults
- Author
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Joe Cohen, Ashley J. Birkett, Marc Lievens, Austin Chhoeu, Gerald Voss, Martha Sedegah, Kristopher M. Paolino, Rich Weltzin, W. Ripley Ballou, Jitta Murphy, Philippe Moris, Erik Jongert, Jerold Sadoff, Maria Grazia Pau, April K. Kathcart, Dirk Heerwegh, James E. Moon, Christian F. Ockenhouse, Yolanda Guerra Mendoza, Ulrike Wille-Reece, Thomas K Oliver, Cynthia Lee, Jenny Hendriks, Jack Komisar, Kirsten E. Lyke, Yannick Vanloubbeeck, Jason A. Regules, James F. Cummings, Johan Vekemans, Donna Tosh, Edwin Kamau, Matthew B. Laurens, Jessica Cowden, and Isabella Versteege
- Subjects
CD4-Positive T-Lymphocytes ,Immunization, Secondary ,Antibodies, Protozoan ,lcsh:Medicine ,Immunologic Tests ,Biology ,law.invention ,Interferon-gamma ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Malaria Vaccines ,medicine ,Humans ,030212 general & internal medicine ,lcsh:Science ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Vaccination ,lcsh:R ,RTS,S ,medicine.disease ,Vaccine efficacy ,Confidence interval ,Malaria ,3. Good health ,Clinical trial ,Titer ,Sporozoites ,Immunoglobulin G ,Antibody Formation ,Immunology ,lcsh:Q ,Research Article - Abstract
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
- Published
- 2015