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

Carly M Bliss,Ya Jankey Jagne,Issa Nébié,Katie L Flanagan,Beate Kampmann,Mireille Ouedraogo,Georgina Bowyer,Kalifa Bojang,Alison M Lawrie,Casimir Tarama,Jean Baptiste Yaro,Uche J Adetifa,Sodiomon B Sirima,Nicola K Viebig,Muhammed O Afolabi,Guillaume S Sanou,Jainaba Njie-Jobe,Odile Leroy,Abdoulie Drammeh,Riccardo Cortese,Rachel Roberts,Amidou Diarra,Alfred B Tiono,Susanne H Hodgson,Nick J Edwards,Nicholas Anagnostou ,Christopher J A Duncan ,Adrian V S Hill ,Oumarou Ouédraogo ,Nicolas Ouédraogo ,Egeruan Babatunde Imoukhuede ,Katie Ewer

doi:10.1016/j.ymthe.2016.11.003

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.

Highlights

Vaccination is one of the most cost-effective health care interventions available, and currently used vaccines prevent an estimated 2.5 million deaths each year.[1]
We have previously described vaccination approaches employing the sporozoite antigen thrombospondin-related adhesion protein (TRAP) fused to a multiple epitope string (ME) in a number of delivery platforms including DNA and replication-deficient viral vectors.[28]
Immunogenicity T Cell Responses Assessed by ELISpot We report elsewhere ex vivo IFNg ELISpot responses stratified by age and dose in group 1 and group median response data stratified by dose in groups 2, 3, and 4.40 Peak ELISpot responses were compared www.moleculartherapy.org between groups in these age de-escalation studies with those from previously published adult phase I trials in the United Kingdom[34] and The Gambia.[32]

Summary

Introduction

Vaccination is one of the most cost-effective health care interventions available, and currently used vaccines prevent an estimated 2.5 million deaths each year.[1] Most vaccines are administered during infancy and protect primarily through the induction of antibodies.[2,3]. There is a range of diseases affecting infants, for which vaccines are yet to be developed, where an ability to induce potent CD8+ T cell responses could be important. An extensive literature in murine immunology documents frequent reductions in CD8+ T cell induction in newborn mice, suggesting that generation of such T cell responses in human infants might be difficult.[5,6,7,8] Limited studies in infants demonstrate reduced Th1 and proliferative responses to vaccination;[9,10,11] data are lacking on the capacity to induce CD8+ T cells in early infancy

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Conclusion