Ad35.CS.01 - RTS,S/AS01 heterologous prime boost vaccine efficacy against sporozoite challenge in healthy malaria-naïve adults

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. © 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.