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Humoral immunogenicity of ChAd63_MVA ME-TRAP vaccination in African infants and children
© Bowyer et al; licensee BioMed Central Ltd. 2014
Published: 22 September 2014
The only malaria vaccine to have been tested in Phase III clinical vaccine trials  induces protection which has been associated with high titres of antibodies against sporozoites. Efficacy against clinical malaria in infants of 5-17 months and 6-12 weeks was 55.8% and 31.3% respectively. A successful malaria vaccine will likely need to induce both cellular and humoral immunity in order to achieve a deployable level of efficacy in the target age groups. Prime-boost immunisation with viral vectors ChAd63 and MVA, both encoding ME-TRAP, has been shown to induce high T cell responses and modest antibody responses to the pre-erythrocytic malaria antigen TRAP. A Phase II study with this vaccine regime in malaria-naïve adults showed significant efficacy, which correlated with frequency of monofunctional CD8+ T cells secreting IFNγ. TRAP antibody titres were modest and did not correlate with protection . In contrast to this, high titres of vaccine-induced anti-TRAP antibodies are measured in infants in malaria-endemic settings.
Materials and methods
Antibody titres were measured in 138 malaria-exposed children vaccinated with ChAd63 MVA ME-TRAP in three Phase I studies in The Gambia and Burkina Faso. Age groups at first immunisation were 2-6 years, 5-12 months and 10 weeks in The Gambia and 5-17 months in Burkina Faso. Avidity and isotype profiles were also analyzed.
Antibody responses to TRAP were significantly higher in 10 week old and 5-12 month old infants in The Gambia and 5-17 month old infants in Burkina Faso compared to 2-6 year old children and adults in The Gambia and malaria-naïve UK adults. IgG isotype responses were predominantly IgG1 and IgG3 and we also detected IgA and IgM. TRAP-specific IgG avidity was significantly higher in Burkinabe infants aged 5-17 months and Gambian infants aged 5-12 months compared to Gambian adults and 2-6 year old children. TRAP-specific IgG1 avidity significantly correlated with age at vaccination in 5-17 month old Burkinabe infants and was significantly higher than in 10 week old Gambian infants. Functional activity of anti-TRAP antibodies will be analysed in vitro using a sporozoite invasion inhibition assay.
We demonstrate excellent humoral immunogenicity in key target populations vaccinated with a pre-erythrocytic malaria vaccination regime, exceeding that seen in UK malaria-naïve adults.
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