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Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants

Lookup NU author(s): Dr Christopher Duncan

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine.


Publication metadata

Author(s): Bliss CM, Drammeh A, Bowyer G, Sanou GS, Jagne YJ, Ouedraogo O, Edwards NJ, Tarama C, Ouedraogo N, Ouedraogo M, NjieJobe J, Diarra A, Afolabi MO, Tiono AB, Yaro JB, Adetifa UJ, Hodgson SH, Anagnostou NA, Roberts R, Duncan CJ, Cortese R, Viebig NK, Leroy O, Lawrie AM, Flanagan KL, Kampmann B, Imoukhuede EB, Sirima SB, Bojang K, Hill AV, Nebie I, Ewer KJ

Publication type: Article

Publication status: Published

Journal: Molecular Therapy

Year: 2017

Volume: 25

Issue: 2

Pages: 547-559

Print publication date: 01/02/2017

Online publication date: 14/12/2016

Acceptance date: 15/11/2016

Date deposited: 22/03/2018

ISSN (print): 1525-0016

ISSN (electronic): 1525-0024

Publisher: Cell Press

URL: https://doi.org/10.1016/j.ymthe.2016.11.003

DOI: 10.1016/j.ymthe.2016.11.003

PubMed id: 28153101


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