Journal
PARASITE IMMUNOLOGY
Volume 43, Issue 12, Pages -Publisher
WILEY
DOI: 10.1111/pim.12877
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Funding
- European Commission [34]
- Chica and Heinz Schaller Foundation [ANR-11-LABX-0024]
- Royal Society [UF0762736, UF120026, RG130034]
- National Centre for the Replacement, Refinement & Reduction of Animals in Research [NC/L000601/1]
- Royal Society [UF120026, UF0762736] Funding Source: Royal Society
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The contribution of antigens expressed during liver stage development to immunity is unclear, and prioritizing antigens for vaccine development based solely on immunogenicity may be limited.
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.
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