Inferior T cell immunogenicity of a Plasmodium berghei model liver stage antigen expressed throughout pre‐erythrocytic maturation

Gibbins, M. P. , Müller, K., Matuschewski, K., Silvie, O. and Clemence R. Hafalla, J. (2021) Inferior T cell immunogenicity of a Plasmodium berghei model liver stage antigen expressed throughout pre‐erythrocytic maturation. Parasite Immunology, 43(12), e12877. (doi: 10.1111/pim.12877) (PMID:34515999)

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Sporozoite antigens are the basis of a number of malaria vaccines being tested, but the contribution of antigens expressed during subsequent liver stage development to pre-erythrocytic stage immunity is poorly understood. We previously showed that, following immunisation with radiation attenuated sporozoites (RAS), a model epitope embedded in a sporozoite surface protein elicited robust CD8+ T cell responses, whilst the same epitope in a liver stage antigen induced inferior responses. Since RAS arrest early in their development in host hepatocytes, we hypothesised that extending parasite maturation in the liver could considerably improve the epitope-specific CD8+ T cell response. Here, we employed a late liver stage arrested parasite model, azithromycin prophylaxis alongside live sporozoites, to increase expression of the model epitope until full liver stage maturation. Strikingly, this alternative immunisation strategy, which has been shown to elicit superior protection, failed to improve the resulting epitope-specific CD8+ T cell responses. Our findings support the notion that liver stage antigens are poorly immunogenic and provide additional caution about prioritising antigens for vaccine development based solely on immunogenicity.

Item Type:Articles
Additional Information:Funding information: European Commission, Grant/Award Number: #34; Chica and Heinz Schaller Foundation, Grant/Award Number: ANR11-LABX-0024; The Royal Society, Grant/ Award Number: UF0762736, UF120026 and RG130034; National Centre for the Replacement, Refinement & Reduction of Animals in Research, Grant/Award Number: NC/L000601/1.
Glasgow Author(s) Enlighten ID:Gibbins, Dr Matt
Authors: Gibbins, M. P., Müller, K., Matuschewski, K., Silvie, O., and Clemence R. Hafalla, J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Parasite Immunology
ISSN (Online):1365-3024
Published Online:13 September 2021
First Published:First published in Parasite Immunology
Publisher Policy:Reproduced under a Creative Commons license

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