Viral vector malaria vaccines induce high-level T cell and antibody responses in West African children and infants
Author(s)
Type
Journal Article
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.
Date Issued
2016-12-14
Date Acceptance
2016-11-15
Citation
Molecular Therapy, 2016, 25 (2), pp.547-559
ISSN
1525-0016
Publisher
Elsevier (Cell Press)
Start Page
547
End Page
559
Journal / Book Title
Molecular Therapy
Volume
25
Issue
2
Copyright Statement
© 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000397307900025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Genetics & Heredity
Medicine, Research & Experimental
Research & Experimental Medicine
MVA ME-TRAP
PLASMODIUM-FALCIPARUM
CIRCUMSPOROZOITE PROTEIN
EARLY-LIFE
INFECTION
IMMUNIZATION
VACCINATION
EFFICACY
AGE
ANTIGEN
Publication Status
Published