Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Safety and high level efficacy of the combination malaria vaccine regimen of RTS,S/AS01B with chimpanzee adenovirus 63 and modified vaccinia ankara vectored vaccines expressing ME-TRAP

Rampling, Tommy, Ewer, Katie J., Bowyer, Georgina, Bliss, Carly M., Edwards, Nick J., Wright, Danny, Payne, Ruth O., Venkatraman, Navin, de Barra, Eoghan, Snudden, Claudia M., Poulton, Ian D., de Graaf, Hans, Sukhtankar, Priya, Roberts, Rachel, Ivinson, Karen, Weltzin, Rich, Rajkumar, Bebi-Yassin, Wille-Reece, Ulrike, Lee, Cynthia K., Ockenhouse, Christian F., Sinden, Robert E., Gerry, Stephen, Lawrie, Alison M., Vekemans, Johan, Morelle, Danielle, Lievens, Marc, Ballou, Ripley W., Cooke, Graham S., Faust, Saul N., Gilbert, Sarah and Hill, Adrian V. S. 2016. Safety and high level efficacy of the combination malaria vaccine regimen of RTS,S/AS01B with chimpanzee adenovirus 63 and modified vaccinia ankara vectored vaccines expressing ME-TRAP. Journal of Infectious Diseases 214 (5) , pp. 772-781. 10.1093/infdis/jiw244

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (896kB)

Abstract

Background. The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector. Method. Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara–vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls. Results. No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected. Conclusions. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: University of Chicago Press / Oxford University Press (OUP): Policy A1 - Oxford Open Option C
ISSN: 0022-1899
Date of First Compliant Deposit: 6 January 2021
Date of Acceptance: 6 June 2016
Last Modified: 06 Jan 2021 12:15
URI: http://orca.cardiff.ac.uk/id/eprint/137197

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics