학술논문
Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults.
Document Type
article
Author
Christian F Ockenhouse; Jason Regules; Donna Tosh; Jessica Cowden; April Kathcart; James Cummings; Kristopher Paolino; James Moon; Jack Komisar; Edwin Kamau; Thomas Oliver; Austin Chhoeu; Jitta Murphy; Kirsten Lyke; Matthew Laurens; Ashley 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; Gerald Voss; W Ripley Ballou; Johan Vekemans
Source
PLoS ONE, Vol 10, Iss 7, p e0131571 (2015)
Subject
Language
English
ISSN
1932-6203
Abstract
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.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).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.ClinicalTrials.gov NCT01366534.