The University of Southampton
University of Southampton Institutional Repository

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

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

1525-0016
2355-2368
Sheehy, Susanne H.
450b85dd-815f-40fa-9458-1ff0f1e85b3a
Duncan, Christopher J. A.
3d260353-99a0-42ee-b45e-4a4bfaec00e6
Elias, Sean C.
28d2a036-b258-40e2-a405-fd82219e6128
Choudhary, Prateek
49fcc20c-af79-4418-aba1-7698b7266a10
Biswas, Sumi
1e555ade-3c02-4264-882f-9c690a50e3cc
Halstead, Fenella D.
66c0fe7d-7b97-4345-8b44-713cfa6da00a
Collins, Katharine A.
c060e119-eab1-4b62-99eb-5a85bb8250dc
Edwards, Nick J.
6bd8bfc4-1441-427e-b5a3-c95a1268c1ce
Douglas, Alexander D.
4a36fda5-7537-4725-9e5f-288b7a43625a
Anagnostou, Nicholas A.
cf0f8162-6e1e-4862-8b35-1d36dd206b9d
Ewer, Katie J.
069f04d6-b524-45c7-ad26-ac830b990860
Havelock, Tom
8f9aa3be-a768-4a7b-bcd4-79656e2b188c
Mahungu, Tabitha
317f36a9-c0c9-4e8d-a25f-8fe2cbc7083f
Bliss, Carly M.
2c3b1866-0931-403d-aef6-27ea51edc10f
Miura, Kazutoyo
37aa1488-b065-4302-b465-25b2c6dcb5b1
Poulton, Ian D.
ae541b7b-11d4-44c3-9b40-d14d291f0b8a
Lillie, Patrick J.
3068afd9-e2bd-4c75-8ad3-e95b412f3456
Antrobus, Richard D.
4594ef62-068c-4685-8488-2ad502cf39d6
Berrie, Eleanor
ef0ff57f-749d-468e-9126-d8732af35518
Moyle, Sarah
b450c00b-5675-4ddb-8c05-4e680f4f8c96
Gantlett, Katherine
c9c7b207-698f-4c08-a26d-9b758fbaef7e
Colloca, Stefano
612948fa-7fba-4c5d-b8a9-83aa62c0cf63
Cortese, Riccardo
48ba5ad5-6b6d-4f08-83f2-5e4d03081d74
Long, Carole A.
e5aca5f4-0941-4939-9d45-649e36f197ae
Sinden, Robert E.
f4124e75-9708-4e9c-a247-f94ea01b3389
Gilbert, Sarah C.
10c23e1c-6e46-4fe8-ae0b-3a1f5cf074f4
Lawrie, Alison M.
dd354ff4-6d60-4029-af83-ae6d233eb2af
Doherty, Tom
a8cd7f78-7823-47d7-9d8f-faa0cee885b4
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Nicosia, Alfredo
7f2fd87b-2018-4b53-8792-ea1d202d32b7
Hill, Adrian V. S.
1d0fcf95-c251-4317-b4b9-f93db4cb8806
Draper, Simon J.
9af827a0-83ed-4fdc-bacc-ff395150d11f
Sheehy, Susanne H.
450b85dd-815f-40fa-9458-1ff0f1e85b3a
Duncan, Christopher J. A.
3d260353-99a0-42ee-b45e-4a4bfaec00e6
Elias, Sean C.
28d2a036-b258-40e2-a405-fd82219e6128
Choudhary, Prateek
49fcc20c-af79-4418-aba1-7698b7266a10
Biswas, Sumi
1e555ade-3c02-4264-882f-9c690a50e3cc
Halstead, Fenella D.
66c0fe7d-7b97-4345-8b44-713cfa6da00a
Collins, Katharine A.
c060e119-eab1-4b62-99eb-5a85bb8250dc
Edwards, Nick J.
6bd8bfc4-1441-427e-b5a3-c95a1268c1ce
Douglas, Alexander D.
4a36fda5-7537-4725-9e5f-288b7a43625a
Anagnostou, Nicholas A.
cf0f8162-6e1e-4862-8b35-1d36dd206b9d
Ewer, Katie J.
069f04d6-b524-45c7-ad26-ac830b990860
Havelock, Tom
8f9aa3be-a768-4a7b-bcd4-79656e2b188c
Mahungu, Tabitha
317f36a9-c0c9-4e8d-a25f-8fe2cbc7083f
Bliss, Carly M.
2c3b1866-0931-403d-aef6-27ea51edc10f
Miura, Kazutoyo
37aa1488-b065-4302-b465-25b2c6dcb5b1
Poulton, Ian D.
ae541b7b-11d4-44c3-9b40-d14d291f0b8a
Lillie, Patrick J.
3068afd9-e2bd-4c75-8ad3-e95b412f3456
Antrobus, Richard D.
4594ef62-068c-4685-8488-2ad502cf39d6
Berrie, Eleanor
ef0ff57f-749d-468e-9126-d8732af35518
Moyle, Sarah
b450c00b-5675-4ddb-8c05-4e680f4f8c96
Gantlett, Katherine
c9c7b207-698f-4c08-a26d-9b758fbaef7e
Colloca, Stefano
612948fa-7fba-4c5d-b8a9-83aa62c0cf63
Cortese, Riccardo
48ba5ad5-6b6d-4f08-83f2-5e4d03081d74
Long, Carole A.
e5aca5f4-0941-4939-9d45-649e36f197ae
Sinden, Robert E.
f4124e75-9708-4e9c-a247-f94ea01b3389
Gilbert, Sarah C.
10c23e1c-6e46-4fe8-ae0b-3a1f5cf074f4
Lawrie, Alison M.
dd354ff4-6d60-4029-af83-ae6d233eb2af
Doherty, Tom
a8cd7f78-7823-47d7-9d8f-faa0cee885b4
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Nicosia, Alfredo
7f2fd87b-2018-4b53-8792-ea1d202d32b7
Hill, Adrian V. S.
1d0fcf95-c251-4317-b4b9-f93db4cb8806
Draper, Simon J.
9af827a0-83ed-4fdc-bacc-ff395150d11f

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), 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.

Full text not available from this repository.

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 Feb 2021 17:07

Export record

Altmetrics

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

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×