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

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, Grobbelaar, Amy, Davies, Huw, Roberts, Rachel, Angus, Brian, Ivinson, Karen, Weltzin, Rich, Rajkumar, Bebi-Yassin, Wille-Reece, Ulrike, Lee, Cynthia, Ockenhouse, Chris, Sinden, Robert E., Gerry, Stephen C., Lawrie, Alison M., Vekemans, Johan, Morelle, Danielle, Lievens, Marc, Ballou, Ripley W., Lewis, David J. M., Cooke, Graham S., Faust, Saul N., Gilbert, Sarah 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 (1) , 49. 10.1038/s41541-018-0084-2

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
ISSN:	2059-0105
Date of First Compliant Deposit:	5 January 2021
Date of Acceptance:	4 September 2018
Last Modified:	03 May 2023 15:50
URI:	https://orca.cardiff.ac.uk/id/eprint/137191

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