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

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

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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.

Original languageEnglish
Article number49
Journalnpj Vaccines
Volume3
Issue number1
DOIs
StatePublished - 1 Dec 2018
Externally publishedYes

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