TY - JOUR
T1 - Ad35.CS.01 - RTS,S/AS01 heterologous prime boost vaccine efficacy against sporozoite challenge in healthy malaria-naïve adults
AU - Ockenhouse, Christian F.
AU - Regules, Jason
AU - Tosh, Donna
AU - Cowden, Jessica
AU - Kathcart, April
AU - Cummings, James
AU - Paolino, Kristopher
AU - Moon, James
AU - Komisar, Jack
AU - Kamau, Edwin
AU - Oliver, Thomas
AU - Chhoeu, Austin
AU - Murphy, Jitta
AU - Lyke, Kirsten
AU - Laurens, Matthew
AU - Birkett, Ashley
AU - Lee, Cynthia
AU - Weltzin, Rich
AU - Wille-Reece, Ulrike
AU - Sedegah, Martha
AU - Hendriks, Jenny
AU - Versteege, Isabella
AU - Pau, Maria Grazia
AU - Sadoff, Jerold
AU - Vanloubbeeck, Yannick
AU - Lievens, Marc
AU - Heerwegh, Dirk
AU - Moris, Philippe
AU - Mendoza, Yolanda Guerra
AU - Jongert, Erik
AU - Cohen, Joe
AU - Voss, Gerald
AU - Ballou, W. Ripley
AU - Vekemans, Johan
N1 - Publisher Copyright:
© 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2015/7/6
Y1 - 2015/7/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84940173032&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0131571
DO - 10.1371/journal.pone.0131571
M3 - Article
C2 - 26148007
AN - SCOPUS:84940173032
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e0131571
ER -