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  • Translating the immunogenicity of prime-boost immunization with ChAd63 and MVA ME-TRAP from malaria naive to malaria-endemic populations.

Translating the immunogenicity of prime-boost immunization with ChAd63 and MVA ME-TRAP from malaria naive to malaria-endemic populations.

Molecular therapy : the journal of the American Society of Gene Therapy (2014-06-17)
Domtila Kimani, Ya Jankey Jagne, Momodou Cox, Eva Kimani, Carly M Bliss, Evelyn Gitau, Caroline Ogwang, Muhammed O Afolabi, Georgina Bowyer, Katharine A Collins, Nick Edwards, Susanne H Hodgson, Christopher J A Duncan, Alexandra J Spencer, Miguel G Knight, Abdoulie Drammeh, Nicholas A Anagnostou, Eleanor Berrie, Sarah Moyle, Sarah C Gilbert, Peninah Soipei, Joseph Okebe, Stefano Colloca, Riccardo Cortese, Nicola K Viebig, Rachel Roberts, Alison M Lawrie, Alfredo Nicosia, Egeruan B Imoukhuede, Philip Bejon, Roma Chilengi, Kalifa Bojang, Katie L Flanagan, Adrian V S Hill, Britta C Urban, Katie J Ewer
ABSTRACT

To induce a deployable level of efficacy, a successful malaria vaccine would likely benefit from both potent cellular and humoral immunity. These requirements are met by a heterologous prime-boost immunization strategy employing a chimpanzee adenovirus vector followed by modified vaccinia Ankara (MVA), both encoding the pre-erythrocytic malaria antigen ME-thrombospondin-related adhesive protein (TRAP), with high immunogenicity and significant efficacy in UK adults. We undertook two phase 1b open-label studies in adults in Kenya and The Gambia in areas of similar seasonal malaria transmission dynamics and have previously reported safety and basic immunogenicity data. We now report flow cytometry and additional interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) data characterizing pre-existing and induced cellular immunity as well as anti-TRAP IgG responses. T-cell responses induced by vaccination averaged 1,254 spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) across both trials and flow cytometry revealed cytokine production from both CD4(+) and CD8(+) T cells with the frequency of CD8(+) IFN-γ-secreting monofunctional T cells (previously shown to associate with vaccine efficacy) particularly high in Kenyan adults. Immunization with ChAd63 and MVA ME-TRAP induced strong cellular and humoral immune responses in adults living in two malaria-endemic regions of Africa. This prime-boost approach targeting the pre-erythrocytic stage of the malaria life-cycle is now being assessed for efficacy in a target population.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Diethanolamine, puriss. p.a., ACS reagent, ≥99.0% (GC)
Supelco
Diethanolamine, analytical standard
Sigma-Aldrich
Diethanolamine, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Sodium azide, purum p.a., ≥99.0% (T)
Sigma-Aldrich
Diethanolamine, ACS reagent, ≥98.5%
Sigma-Aldrich
Diethanolamine, reagent grade, ≥98.0%
Sigma-Aldrich
Sodium azide, BioXtra
Sigma-Aldrich
Sodium azide, ReagentPlus®, ≥99.5%
Trolamine impurity B, European Pharmacopoeia (EP) Reference Standard