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Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing CS & ME-TRAP against controlled human malaria infection in malaria naïve individuals

Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing CS & ME-TRAP against controlled human malaria infection in malaria naïve individuals
Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing CS & ME-TRAP against controlled human malaria infection in malaria naïve individuals
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 ChAd63-MVA is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the pre-erythrocytic antigen insert ME-TRAP. We hypothesised that ChAd63-MVA containing CS may result in significant, clinical protective efficacy.

Methods.?We conducted an open-label, two-site partially randomized sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. The study was registered at: www.clinicaltrials.gov (NCT01623557).

Results.?1/15 (7%) vaccinees receiving ChAd63-MVA CS and 2/15 (13%) vaccinees receiving ChAd63-MVA ME-TRAP were sterilely protected post-CHMI. 3/15 (20%) vaccinees receiving ChAd63-MVA CS and 5/15 (33%) vaccinees receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment compared to unvaccinated controls. In qPCR analyses, ChAd63-MVA CS was estimated to reduce liver parasite burden by 69-79%, compared to 79-84% for ChAd63-MVA ME-TRAP.

Conclusions.?ChAd63-MVA CS does result in a reduction in 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
0022-1899
1076-1086
Hodgson, S.H.
f417a194-992a-4263-8f2c-c519eb2a44b6
Ewer, K.J.
c80b1152-51bb-4cbc-a78e-2084abac19af
Bliss, C.M.
c481b91f-68e5-4911-b9cb-8efae22fdc4a
Edwards, N.J.
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Rampling, T.
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Anagnostou, N.A.
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de Barra, E.
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Havelock, T.
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Bowyer, G.
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Poulton, I.D.
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de Cassan, S.
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Illingworth, J.J.
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Douglas, A.D.
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Mange, P.B.
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Collins, K.A.
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Roberts, R.
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Gerry, S.
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Berrie, E.
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Moyle, S.
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Colloca, S.
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Cortese, R.
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Sinden, R.E.
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Gilbert, S.C.
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Bejon, P.
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Lawrie, A.M.
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Nicosia, A.
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Faust, S.N .
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Hill, A.V.
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Hodgson, S.H.
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Ewer, K.J.
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Bliss, C.M.
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Edwards, N.J.
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Rampling, T.
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Anagnostou, N.A.
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de Barra, E.
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Havelock, T.
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Bowyer, G.
41917953-374d-479e-a0ce-664833e32979
Poulton, I.D.
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de Cassan, S.
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Illingworth, J.J.
c8ddd921-30cb-4135-b484-9261a907866d
Douglas, A.D.
2013ebf4-302a-411a-8a57-5a164efe21c1
Mange, P.B.
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Collins, K.A.
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Roberts, R.
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Gerry, S.
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Berrie, E.
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Moyle, S.
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Colloca, S.
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Cortese, R.
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Sinden, R.E.
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Gilbert, S.C.
59445e39-22af-490c-ab8e-1d4fc27b9828
Bejon, P.
0403ec62-7c89-436d-aa9c-572aafbcecbb
Lawrie, A.M.
786384af-815b-4e26-821e-52582c8fa86c
Nicosia, A.
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Faust, S.N .
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Hill, A.V.
d9af9241-5268-422d-928e-d76e7ef9b121

Hodgson, S.H., Ewer, K.J., Bliss, C.M., Edwards, N.J., Rampling, T., Anagnostou, N.A., de Barra, E., Havelock, T., Bowyer, G., Poulton, I.D., de Cassan, S., Illingworth, J.J., Douglas, A.D., Mange, P.B., Collins, K.A., Roberts, R., Gerry, S., Berrie, E., Moyle, S., Colloca, S., Cortese, R., Sinden, R.E., Gilbert, S.C., Bejon, P., Lawrie, A.M., Nicosia, A., Faust, S.N . and Hill, A.V. (2015) Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing CS & ME-TRAP against controlled human malaria infection in malaria naïve individuals. The Journal of Infectious Diseases, 211 (7), 1076-1086. (doi:10.1093/infdis/jiu579). (PMID:25336730)

Record type: Article

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 ChAd63-MVA is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the pre-erythrocytic antigen insert ME-TRAP. We hypothesised that ChAd63-MVA containing CS may result in significant, clinical protective efficacy.

Methods.?We conducted an open-label, two-site partially randomized sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. The study was registered at: www.clinicaltrials.gov (NCT01623557).

Results.?1/15 (7%) vaccinees receiving ChAd63-MVA CS and 2/15 (13%) vaccinees receiving ChAd63-MVA ME-TRAP were sterilely protected post-CHMI. 3/15 (20%) vaccinees receiving ChAd63-MVA CS and 5/15 (33%) vaccinees receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment compared to unvaccinated controls. In qPCR analyses, ChAd63-MVA CS was estimated to reduce liver parasite burden by 69-79%, compared to 79-84% for ChAd63-MVA ME-TRAP.

Conclusions.?ChAd63-MVA CS does result in a reduction in 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

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J Infect Dis.-2014-Hodgson-infdis_jiu579.pdf - Accepted Manuscript
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Published date: 1 April 2015
Organisations: Faculty of Medicine

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Local EPrints ID: 371775
URI: https://eprints.soton.ac.uk/id/eprint/371775
ISSN: 0022-1899
PURE UUID: 1fc89e4e-4159-403d-8cb5-caa2025d9ce9
ORCID for S.N . Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 13 Nov 2014 17:02
Last modified: 29 Aug 2019 00:42

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Contributors

Author: S.H. Hodgson
Author: K.J. Ewer
Author: C.M. Bliss
Author: N.J. Edwards
Author: T. Rampling
Author: N.A. Anagnostou
Author: E. de Barra
Author: T. Havelock
Author: G. Bowyer
Author: I.D. Poulton
Author: S. de Cassan
Author: J.J. Illingworth
Author: A.D. Douglas
Author: P.B. Mange
Author: K.A. Collins
Author: R. Roberts
Author: S. Gerry
Author: E. Berrie
Author: S. Moyle
Author: S. Colloca
Author: R. Cortese
Author: R.E. Sinden
Author: S.C. Gilbert
Author: P. Bejon
Author: A.M. Lawrie
Author: A. Nicosia
Author: S.N . Faust ORCID iD
Author: A.V. Hill

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