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


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.

SUBMITTER: Bliss CM 

PROVIDER: S-EPMC5368405 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Bliss Carly M CM   Drammeh Abdoulie A   Bowyer Georgina G   Sanou Guillaume S GS   Jagne Ya Jankey YJ   Ouedraogo Oumarou O   Edwards Nick J NJ   Tarama Casimir C   Ouedraogo Nicolas N   Ouedraogo Mireille M   Njie-Jobe Jainaba J   Diarra Amidou A   Afolabi Muhammed O MO   Tiono Alfred B AB   Yaro Jean Baptiste JB   Adetifa Uche J UJ   Hodgson Susanne H SH   Anagnostou Nicholas A NA   Roberts Rachel R   Duncan Christopher J A CJ   Cortese Riccardo R   Viebig Nicola K NK   Leroy Odile O   Lawrie Alison M AM   Flanagan Katie L KL   Kampmann Beate B   Imoukhuede Egeruan B EB   Sirima Sodiomon B SB   Bojang Kalifa K   Hill Adrian V S AV   Nébié Issa I   Ewer Katie J KJ  

Molecular therapy : the journal of the American Society of Gene Therapy 20170201 2


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<sup>+</sup> 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- t  ...[more]

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