Lookup NU author(s): Dr Christopher Duncan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
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
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
PubMed id: 28153101
Altmetrics provided by Altmetric