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

Abstract

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.

• Authors: Muhammed O Afolabi, Alfred B Tiono, Uche J Adetifa, Jean Baptiste Yaro, Abdoulie Drammeh, Issa Nébié, Carly Bliss, Susanne H Hodgson, Nicholas A Anagnostou, Guillaume S Sanou, Ya Jankey Jagne, Oumarou Ouedraogo, Casimir Tamara, Nicolas Ouedraogo, Mirielle Ouedraogo, Jainaba Njie-Jobe, Amidou Diarra, Christopher Ja Duncan, Riccardo Cortese, Alfredo Nicosia, Rachel Roberts, Nicola K Viebig, Odile Leroy, Alison M Lawrie, Katie L Flanagan, Beate Kampman, Philip Bejon, Egeruan B Imoukhuede, Katie J Ewer, Adrian Vs Hill, Kalifa Bojang, Sodiomon B Sirima
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 24 Issue 8 Pg. 1470-7 (Aug 2016) ISSN: 1525-0024 [Electronic] United States
• PMID: 27109630 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antibodies, Protozoan
• Epitopes
• Malaria Vaccines

Topics

• Adenoviruses, Simian
• Africa, Western (epidemiology)
• Animals
• Antibodies, Protozoan (blood, immunology)
• Child
• Child, Preschool
• Enzyme-Linked Immunospot Assay
• Epitopes (immunology)
• Gambia
• Genetic Vectors (adverse effects)
• Humans
• Immunization, Secondary
• Infant
• Infant, Newborn
• Malaria (epidemiology, prevention & control)
• Malaria Vaccines (administration & dosage, adverse effects, immunology)
• Outcome Assessment, Health Care
• Vaccinia virus