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Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP

Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP
Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP

Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens exhibited acceptable reactogenicity and CD8+ T cell immunogenicity was enhanced with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP vaccination at 4- or 8-weeks (AAM or A-A-M). Induction of TRAP antibodies was comparable between schedules. T cell immunity against the ChAd63 hexon did not affect T cell responses to the vaccine insert, however pre-vaccination ChAd63-specific T cells correlated with reduced TRAP antibodies. Vaccine-induced antibodies against MVA did not affect TRAP antibody induction, and correlated positively with ME-TRAP-specific T cells. This study identifies potentially more effective immunisation regimens to assess in Phase IIa trials and demonstrates a degree of flexibility with the timing of vectored vaccine administration, aiding incorporation into existing vaccination programmes.

2045-2322
Bliss, Carly M.
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Bowyer, Georgina
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Anagnostou, Nicholas A.
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Havelock, Tom
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Snudden, Claudia M.
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Davies, Huw
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De Cassan, Simone C.
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Grobbelaar, Amy
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Lawrie, Alison M.
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Venkatraman, Navin
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Poulton, Ian D.
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Roberts, Rachel
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Mange, Pooja B.
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Choudhary, Prateek
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Faust, Saul N.
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Colloca, Stefano
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Gilbert, Sarah C.
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Nicosia, Alfredo
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Hill, Adrian V.S.
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Ewer, Katie J.
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Bliss, Carly M.
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Bowyer, Georgina
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Anagnostou, Nicholas A.
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Havelock, Tom
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Snudden, Claudia M.
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Davies, Huw
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De Cassan, Simone C.
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Grobbelaar, Amy
a46b5745-bfe2-4a26-8c4d-c26a8a037ada
Lawrie, Alison M.
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Venkatraman, Navin
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Poulton, Ian D.
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Roberts, Rachel
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Mange, Pooja B.
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Choudhary, Prateek
49fcc20c-af79-4418-aba1-7698b7266a10
Faust, Saul N.
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Colloca, Stefano
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Gilbert, Sarah C.
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Nicosia, Alfredo
7f2fd87b-2018-4b53-8792-ea1d202d32b7
Hill, Adrian V.S.
1d0fcf95-c251-4317-b4b9-f93db4cb8806
Ewer, Katie J.
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Bliss, Carly M., Bowyer, Georgina, Anagnostou, Nicholas A., Havelock, Tom, Snudden, Claudia M., Davies, Huw, De Cassan, Simone C., Grobbelaar, Amy, Lawrie, Alison M., Venkatraman, Navin, Poulton, Ian D., Roberts, Rachel, Mange, Pooja B., Choudhary, Prateek, Faust, Saul N., Colloca, Stefano, Gilbert, Sarah C., Nicosia, Alfredo, Hill, Adrian V.S. and Ewer, Katie J. (2018) Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP. Scientific Reports, 8 (1). (doi:10.1038/s41598-018-21630-4).

Record type: Article

Abstract

Heterologous prime-boost vaccination with viral vectors simian adenovirus 63 (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody responses in humans. The 8-week regimen demonstrates significant efficacy against malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin-Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A), multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens exhibited acceptable reactogenicity and CD8+ T cell immunogenicity was enhanced with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP vaccination at 4- or 8-weeks (AAM or A-A-M). Induction of TRAP antibodies was comparable between schedules. T cell immunity against the ChAd63 hexon did not affect T cell responses to the vaccine insert, however pre-vaccination ChAd63-specific T cells correlated with reduced TRAP antibodies. Vaccine-induced antibodies against MVA did not affect TRAP antibody induction, and correlated positively with ME-TRAP-specific T cells. This study identifies potentially more effective immunisation regimens to assess in Phase IIa trials and demonstrates a degree of flexibility with the timing of vectored vaccine administration, aiding incorporation into existing vaccination programmes.

Text s41598-018-21630-4 - Version of Record
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Accepted/In Press date: 7 February 2018
e-pub ahead of print date: 21 February 2018
Published date: 1 December 2018

Identifiers

Local EPrints ID: 418388
URI: https://eprints.soton.ac.uk/id/eprint/418388
ISSN: 2045-2322
PURE UUID: a45cc767-5b7d-4979-9fc6-04c88130f649
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 06 Mar 2018 17:30
Last modified: 14 Dec 2018 01:33

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Contributors

Author: Carly M. Bliss
Author: Georgina Bowyer
Author: Nicholas A. Anagnostou
Author: Tom Havelock
Author: Claudia M. Snudden
Author: Huw Davies
Author: Simone C. De Cassan
Author: Amy Grobbelaar
Author: Alison M. Lawrie
Author: Navin Venkatraman
Author: Ian D. Poulton
Author: Rachel Roberts
Author: Pooja B. Mange
Author: Prateek Choudhary
Author: Saul N. Faust ORCID iD
Author: Stefano Colloca
Author: Sarah C. Gilbert
Author: Alfredo Nicosia
Author: Adrian V.S. Hill
Author: Katie J. Ewer

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