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

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) , 3390. 10.1038/s41598-018-21630-4

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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.

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/.
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 5 January 2021
Date of Acceptance: 7 February 2018
Last Modified: 05 Jan 2021 16:15
URI: http://orca.cardiff.ac.uk/id/eprint/137192

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