Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.
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.
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
Carly M
CM
Bliss
Medical Research Council Unit, Fajara, The Gambia.
Abdoulie
A
Drammeh
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
Georgina
G
Bowyer
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Guillaume S
GS
Sanou
Medical Research Council Unit, Fajara, The Gambia.
Ya Jankey
YJ
Jagne
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Oumarou
O
Ouedraogo
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
Nick J
NJ
Edwards
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Casimir
C
Tarama
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Nicolas
N
Ouedraogo
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Mireille
M
Ouedraogo
Medical Research Council Unit, Fajara, The Gambia.
Jainaba
J
Njie-Jobe
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Amidou
A
Diarra
Medical Research Council Unit, Fajara, The Gambia.
Muhammed O
MO
Afolabi
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Alfred B
AB
Tiono
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Jean Baptiste
JB
Yaro
Medical Research Council Unit, Fajara, The Gambia.
Uche J
UJ
Adetifa
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Susanne H
SH
Hodgson
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Nicholas A
NA
Anagnostou
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Rachel
R
Roberts
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Christopher J A
CJ
Duncan
Keires AG, Baumleingasse 18, 4051 Basel, Switzerland.
Riccardo
R
Cortese
European Vaccine Initiative, Universitäts Klinikum Heidelberg, Voßstr. 2, 69115 Heidelberg, Germany.
Nicola K
NK
Viebig
European Vaccine Initiative, Universitäts Klinikum Heidelberg, Voßstr. 2, 69115 Heidelberg, Germany.
Odile
O
Leroy
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Alison M
AM
Lawrie
Medical Research Council Unit, Fajara, The Gambia.
Katie L
KL
Flanagan
Medical Research Council Unit, Fajara, The Gambia; Department of Paediatrics, Imperial College London SW7 2AZ, UK.
Beate
B
Kampmann
Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Egeruan B
EB
Imoukhuede
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Sodiomon B
SB
Sirima
Medical Research Council Unit, Fajara, The Gambia.
Kalifa
K
Bojang
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK; Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford OX3 7LE, UK.
Adrian V S
AV
Hill
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, 01 BP 2208 Ouagadougou, Burkina Faso.
Issa
I
Nébié
The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK. Electronic address: katie.ewer@ndm.ox.ac.uk.
Katie J
KJ
Ewer
D000354:Africa, Western; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
D000913:Antibodies, Protozoan; D007132:Immunoglobulin Isotypes; D017780:Malaria Vaccines
Phase I trial; T cells; antibodies; malaria; vaccine; viral vectors