Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporo...

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Bibliographic Details
Published in:	Molecular therapy Vol. 24; no. 8; pp. 1470 - 1477
Main Authors:	Afolabi, Muhammed O, Tiono, Alfred B, Adetifa, Uche J, Yaro, Jean Baptiste, Drammeh, Abdoulie, Nébié, Issa, Bliss, Carly, Hodgson, Susanne H, Anagnostou, Nicholas A, Sanou, Guillaume S, Jagne, Ya Jankey, Ouedraogo, Oumarou, Tamara, Casimir, Ouedraogo, Nicolas, Ouedraogo, Mirielle, Njie-Jobe, Jainaba, Diarra, Amidou, Duncan, Christopher JA, Cortese, Riccardo, Nicosia, Alfredo, Roberts, Rachel, Viebig, Nicola K, Leroy, Odile, Lawrie, Alison M, Flanagan, Katie L, Kampman, Beate, Bejon, Philip, Imoukhuede, Egeruan B, Ewer, Katie J, Hill, Adrian VS, Bojang, Kalifa, Sirima, Sodiomon B
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-08-2016 Elsevier Limited Nature Publishing Group
Subjects:	Adenovirus Adenoviruses Adenoviruses, Simian Africa, Western - epidemiology Age Animals Antibodies, Protozoan - blood Antibodies, Protozoan - immunology Child Child, Preschool Drug dosages Enzyme-Linked Immunospot Assay Epitopes - immunology Gambia Genetic Vectors - adverse effects Humans Immunization, Secondary Infant Infant, Newborn Malaria Malaria - epidemiology Malaria - prevention & control Malaria Vaccines - administration & dosage Malaria Vaccines - adverse effects Malaria Vaccines - immunology Medical research Monkeys & apes Original Outcome Assessment, Health Care Pan troglodytes Rabies Tropical diseases Vaccines Vaccinia virus Gambia Africa, Western Turkey Burkina Faso United Kingdom > UK Africa Ankara Turkey Italy
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Summary:	Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2–6 years old in The Gambia; 5–17 months old in Burkina Faso; 5–12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The first two authors and the last two authors contributed equally to this work.
ISSN:	1525-0016 1525-0024
DOI:	10.1038/mt.2016.83