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ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans

Sheehy, Susanne H., Duncan, Christopher J. A., Elias, Sean C., Choudhary, Prateek, Biswas, Sumi, Halstead, Fenella D., Collins, Katharine A., Edwards, Nick J., Douglas, Alexander D., Anagnostou, Nicholas A., Ewer, Katie J., Havelock, Tom, Mahungu, Tabitha, Bliss, Carly M., Miura, Kazutoyo, Poulton, Ian D., Lillie, Patrick J., Antrobus, Richard D., Berrie, Eleanor, Moyle, Sarah, Gantlett, Katherine, Colloca, Stefano, Cortese, Riccardo, Long, Carole A., Sinden, Robert E., Gilbert, Sarah C., Lawrie, Alison M., Doherty, Tom, Faust, Saul N., Nicosia, Alfredo, Hill, Adrian V. S. and Draper, Simon J. (2012) ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans Molecular Therapy, 20, (12), pp. 2355-2368. (doi:10.1038/mt.2012.223). (PMID:23089736).

Record type: Article

Abstract

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1—results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets.

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More information

e-pub ahead of print date: 23 October 2012
Published date: December 2012
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 345972
URI: http://eprints.soton.ac.uk/id/eprint/345972
ISSN: 1525-0016
PURE UUID: d6e60c19-ce52-4537-bdd5-d873483e34fc
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 10 Dec 2012 14:58
Last modified: 18 Jul 2017 05:06

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Contributors

Author: Susanne H. Sheehy
Author: Christopher J. A. Duncan
Author: Sean C. Elias
Author: Prateek Choudhary
Author: Sumi Biswas
Author: Fenella D. Halstead
Author: Katharine A. Collins
Author: Nick J. Edwards
Author: Alexander D. Douglas
Author: Nicholas A. Anagnostou
Author: Katie J. Ewer
Author: Tom Havelock
Author: Tabitha Mahungu
Author: Carly M. Bliss
Author: Kazutoyo Miura
Author: Ian D. Poulton
Author: Patrick J. Lillie
Author: Richard D. Antrobus
Author: Eleanor Berrie
Author: Sarah Moyle
Author: Katherine Gantlett
Author: Stefano Colloca
Author: Riccardo Cortese
Author: Carole A. Long
Author: Robert E. Sinden
Author: Sarah C. Gilbert
Author: Alison M. Lawrie
Author: Tom Doherty
Author: Saul N. Faust ORCID iD
Author: Alfredo Nicosia
Author: Adrian V. S. Hill
Author: Simon J. Draper

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