Dysfunctional memory B cell responses to the protective repeat region of the Plasmodium circumsporozoite protein are associated with waning humoral immunity
McDougal, C. E.; Mkindi, C. G.; Rodda, L. B.; Lucarelli, C. V.; Langowski, M. D.; King, N. P.; Jongo, S.; Daubenberger, C.; Pepper, M.
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Malaria vaccines provide waning protection from disease that is correlated with the production of antibodies to the repeat region of the circumsporozoite protein (CSP). CSP-based vaccines display limited durability in malaria-naive individuals yet are even less effective in malaria-experienced individuals, suggesting the generation of non-optimal humoral immunity in response to both infection and vaccination. To address this hypothesis, we performed a cross-species, comprehensive analysis of B cell responses to CSP after Plasmodium infection or immunization, focusing our analysis on the repeat and C-terminus domains included in malaria subunit vaccines. Herein we demonstrate that the repetitive nature of the protective region of the CSP protein independently impacts the differentiation of the CSP-specific B cells, impinging on their ability to recall for multiple subsequent exposures.
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