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

Autor: Bliss, CM, Drammeh, A, Bowyer, G, Sanou, GS, Jagne, YJ, Ouedraogo, O, Edwards, NJ, Tarama, C, Ouedraogo, N, Ouedraogo, M, Njie-Jobe, J, Diarra, A, Afolabi, MO, Tiono, AB, Yaro, JB, Adetifa, UJ, Hodgson, SH, Anagnostou, NA, Roberts, R, Duncan, CJA, Cortese, R, Viebig, NK, Leroy, O, Lawrie, AM, Flanagan, KL, Kampmann, B, Imoukhuede, EB, Sirima, SB, Bojang, K, Hill, AVS, Nebie, I, Ewer, KJ
Rok vydání: 2017
Předmět:
T-Lymphocytes
Antibodies
Protozoan
Research & Experimental Medicine
10 Technology
vaccine
INFECTION
Drug Discovery
antibodies
Malaria
Falciparum
Child
Genetics & Heredity
MVA ME-TRAP
Immunity
Cellular
PLASMODIUM-FALCIPARUM
Vaccination
11 Medical And Health Sciences
Flow Cytometry
IMMUNIZATION
Immunoglobulin Isotypes
Africa
Western
Medicine
Research & Experimental
Child
Preschool
Molecular Medicine
Original Article
Female
Life Sciences & Biomedicine
Biotechnology
CIRCUMSPOROZOITE PROTEIN
viral vectors
ANTIGEN
Genetic Vectors
Plasmodium falciparum
malaria
T cells
Enzyme-Linked Immunosorbent Assay
EARLY-LIFE
Phase I trial
AGE
Malaria Vaccines
parasitic diseases
Genetics
Humans
Molecular Biology
Pharmacology
Science & Technology
Infant
Newborn
Infant
06 Biological Sciences
EFFICACY
Immunity
Humoral
Biotechnology & Applied Microbiology
Zdroj: Molecular Therapy
ISSN: 1525-0016
DOI: 10.1016/j.ymthe.2016.11.003
Popis: 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.
An effective malaria vaccine is an urgent global health priority. In these studies, Ewer and colleagues describe strong T cell and antibody responses in children and infants following vaccination with a viral vectored vaccine regime encoding a pre-erythrocytic malaria antigen. This regime has previously demonstrated efficacy in adults and these data support assessment of the efficacy of this vaccine in infants.
Databáze: OpenAIRE
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