Translating the Immunogenicity of Prime-boost Immunization With ChAd63 and MVA ME-TRAP From Malaria Naive to Malaria-endemic Populations

Kimani, Domtila, Jagne, Ya Jankey, Cox, Momodou, Kimani, Eva, Bliss, Carly M, Gitau, Evelyn, Ogwang, Caroline, Afolabi, Muhammed O, Bowyer, Georgina, Collins, Katharine A, Edwards, Nick, Hodgson, Susanne H, Duncan, Christopher J A, Spencer, Alexandra J, Knight, Miguel G, Drammeh, Abdoulie, Anagnostou, Nicholas A, Berrie, Eleanor, Moyle, Sarah, Gilbert, Sarah C, Soipei, Peninah, Okebe, Joseph, Colloca, Stefano, Cortese, Riccardo, Viebig, Nicola K, Roberts, Rachel, Lawrie, Alison M, Nicosia, Alfredo, Imoukhuede, Egeruan B, Bejon, Philip, Chilengi, Roma, Bojang, Kalifa, Flanagan, Katie L, Hill, Adrian V S, Urban, Britta ORCID: https://orcid.org/0000-0002-4197-8393 and Ewer, Katie J (2014) 'Translating the Immunogenicity of Prime-boost Immunization With ChAd63 and MVA ME-TRAP From Malaria Naive to Malaria-endemic Populations'. Molecular Therapy, Vol 22, Issue 11, pp. 1992-2003.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 300 General works QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids WA Public Health > Preventive Medicine > WA 115 Immunization WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1038/mt.2014.109
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	13 Apr 2015 09:15
Last Modified:	06 Feb 2018 13:09
URI:	https://archive.lstmed.ac.uk/id/eprint/5073

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