Volume 13 Supplement 1

Challenges in malaria research: Core science and innovation

Open Access

Humoral immunogenicity of ChAd63_MVA ME-TRAP vaccination in African infants and children

  • Georgina Bowyer1,
  • Muhammed O Afolabi2,
  • Carly M Bliss1,
  • Alfred B Tiono3,
  • Abdoulie Drammeh2,
  • Issa Nébié3,
  • Ya Jankey Jagne2,
  • Jean Baptiste Yaro3,
  • Egeruan B Imoukhuede4,
  • Katie L Flanagan2,
  • Beate Kampman2,
  • Nicola Viebig5,
  • Sodiomon B Sirima3,
  • Kalifa Bojang2,
  • Adrian VS Hill1, 4 and
  • Katie J Ewer1
Malaria Journal201413(Suppl 1):P16

https://doi.org/10.1186/1475-2875-13-S1-P16

Published: 22 September 2014

Background

The only malaria vaccine to have been tested in Phase III clinical vaccine trials [1] 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 [2]. 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.

Results

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.

Conclusions

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.

Authors’ Affiliations

(1)
Jenner Institute Laboratories, University of Oxford
(2)
Medical Research Council Unit
(3)
Centre National de Recherche et de Formation sur le Paludisme
(4)
Centre for Clinical Vaccinology and Tropical Medicine
(5)
European Vaccine Initiative

References

  1. Vansadia P: A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants. N Engl J Med. 2012, 367: 2284-2295.View ArticlePubMedGoogle Scholar
  2. Ewer K, O’Hara G: Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun. 2013, 4:Google Scholar

Copyright

© Bowyer et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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