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Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP

Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP
Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP
We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI). Safety and immunogenicity of the vaccine regimen was also assessed. Forty-one malaria-naive adults received RTS,S/AS01B at 0, 4 and 8 weeks, either alone (Groups 1 and 2) or with ChAd63 ME-TRAP at week 0, and modified vaccinia Ankara (MVA) ME-TRAP at weeks 4 and 8 (Groups 3 and 4). Groups 2 and 4 received a fractional (1/5th) dose of RTS,S/AS01B at week 8. CHMI was delivered by mosquito bite 11 weeks after first vaccination. Vaccine efficacy was 6/8 (75%), 8/9 (88.9%), 6/10 (60%), and 5/9 (55.6%) of subjects in Groups 1, 2, 3, and 4, respectively. Immunological analysis indicated significant reductions in anti-circumsporozoite protein antibodies and TRAP-specific T cells at CHMI in the combination vaccine groups. This reduced immunogenicity was only observed after concomitant administration of the third dose of RTS,S/AS01B with the second dose of MVA ME-TRAP. The second dose of the MVA vector with a four-week interval caused significantly higher anti-vector immunity than the first and may have been the cause of immunological interference. Co-administration of ChAd63/MVA ME-TRAP with RTS,S/AS01B led to reduced immunogenicity and efficacy, indicating the need for evaluation of alternative schedules or immunization sites in attempts to generate optimal efficacy.
2059-0105
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De Graaf, Hans
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Morelle, Danielle
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Lewis, David J.M
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Cooke, Graham S.
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Faust, Saul
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Gilbert, Sarah C.
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Rampling, Tommy, Ewer, Katie J., Bowyer, Georgina, Edwards, Nick J., Wright, Danny, Sridhar, Saranya, Payne, Ruth, Powlson, Jonathan, Bliss, Carly, Venkatraman, Navin, Poulton, Ian D., De Graaf, Hans, Gbesemete, Diane, Frances, Grobbelaar, A.O., Davies, Huw, Roberts, Rachel, Angus, Brian, Ivinson, Karen, Weltzin, Rich, Rajkumar, Bebi-Yassin, Wille-Reece, U., Lee, Cynthia, Ockenhouse, Chris, Sinden, Robert E., Gerry, Stephen, Lawrie, Alison M., Vekemans, Johan, Morelle, Danielle, Lievens, Marc, Ballou, Ripley W., Lewis, David J.M, Cooke, Graham S., Faust, Saul, Gilbert, Sarah C. and Hill, Adrian V. S. (2018) Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP. NPJ Vaccines, 3, [49]. (doi:10.1038/s41541-018-0084-2).

Record type: Article

Abstract

We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI). Safety and immunogenicity of the vaccine regimen was also assessed. Forty-one malaria-naive adults received RTS,S/AS01B at 0, 4 and 8 weeks, either alone (Groups 1 and 2) or with ChAd63 ME-TRAP at week 0, and modified vaccinia Ankara (MVA) ME-TRAP at weeks 4 and 8 (Groups 3 and 4). Groups 2 and 4 received a fractional (1/5th) dose of RTS,S/AS01B at week 8. CHMI was delivered by mosquito bite 11 weeks after first vaccination. Vaccine efficacy was 6/8 (75%), 8/9 (88.9%), 6/10 (60%), and 5/9 (55.6%) of subjects in Groups 1, 2, 3, and 4, respectively. Immunological analysis indicated significant reductions in anti-circumsporozoite protein antibodies and TRAP-specific T cells at CHMI in the combination vaccine groups. This reduced immunogenicity was only observed after concomitant administration of the third dose of RTS,S/AS01B with the second dose of MVA ME-TRAP. The second dose of the MVA vector with a four-week interval caused significantly higher anti-vector immunity than the first and may have been the cause of immunological interference. Co-administration of ChAd63/MVA ME-TRAP with RTS,S/AS01B led to reduced immunogenicity and efficacy, indicating the need for evaluation of alternative schedules or immunization sites in attempts to generate optimal efficacy.

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Accepted/In Press date: 4 September 2018
e-pub ahead of print date: 9 October 2018

Identifiers

Local EPrints ID: 430531
URI: http://eprints.soton.ac.uk/id/eprint/430531
ISSN: 2059-0105
PURE UUID: 24207d66-775f-40f3-887e-61aa0cbb50a2
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 03 May 2019 16:30
Last modified: 26 Nov 2021 02:50

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Contributors

Author: Tommy Rampling
Author: Katie J. Ewer
Author: Georgina Bowyer
Author: Nick J. Edwards
Author: Danny Wright
Author: Saranya Sridhar
Author: Ruth Payne
Author: Jonathan Powlson
Author: Carly Bliss
Author: Navin Venkatraman
Author: Ian D. Poulton
Author: Hans De Graaf
Author: Diane, Frances Gbesemete
Author: A.O. Grobbelaar
Author: Huw Davies
Author: Rachel Roberts
Author: Brian Angus
Author: Karen Ivinson
Author: Rich Weltzin
Author: Bebi-Yassin Rajkumar
Author: U. Wille-Reece
Author: Cynthia Lee
Author: Chris Ockenhouse
Author: Robert E. Sinden
Author: Stephen Gerry
Author: Alison M. Lawrie
Author: Johan Vekemans
Author: Danielle Morelle
Author: Marc Lievens
Author: Ripley W. Ballou
Author: David J.M Lewis
Author: Graham S. Cooke
Author: Saul Faust ORCID iD
Author: Sarah C. Gilbert
Author: Adrian V. S. Hill

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