Dataset Information

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

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-? 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.

SUBMITTER: Ockenhouse CF

PROVIDER: S-EPMC4492580 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

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

PloS one 20150706 7

<h4>Methods</h4>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.<h4>Results</h4>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-grou ...[more]

PMID: 26148007