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Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals

Hodgson, Susanne H., Ewer, Katie J., Bliss, Carly M., Edwards, Nick J., Rampling, Thomas, Anagnostou, Nicholas A., de Barra, Eoghan, Havelock, Tom, Bowyer, Georgina, Poulton, Ian D., de Cassan, Simone, Longley, Rhea, Illingworth, Joseph J., Douglas, Alexander D., Mange, Pooja B., Collins, Katharine A., Roberts, Rachel, Gerry, Stephen, Berrie, Eleanor, Moyle, Sarah, Colloca, Stefano, Cortese, Riccardo, Sinden, Robert E., Gilbert, Sarah C., Bejon, Philip, Lawrie, Alison M., Nicosia, Alfredo, Faust, Saul N. and Hill, Adrian V. S. 2015. Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals. Journal of Infectious Diseases 211 (7) , pp. 1076-1086. 10.1093/infdis/jiu579

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Abstract

Background. Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope–thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. Methods. We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. Results. One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%–79%, compared with 79%–84% for ChAd63-MVA ME-TRAP. Conclusions. ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development.

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: 10 October 2014
Last Modified: 06 Jan 2021 13:00
URI: http://orca.cardiff.ac.uk/id/eprint/137203

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