Analysis of human B ‐cell responses following C h A d63‐ MVA MSP 1 and AMA 1 immunization and controlled malaria infection

Acquisition of non‐sterilizing natural immunity to P lasmodium falciparum malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective B ‐cell responses. To date, the impact of blood‐stage parasite exposure on antigen‐specific B cells has not been reported following controlled human malaria infection ( CHMI ). Here we analysed human B ‐cell responses in a series of P hase I/IIa clinical trials, which include CHMI , using candidate virus‐vectored vaccines encoding two blood‐stage antigens: merozoite surface protein 1 ( MSP 1) and apical membrane antigen 1 ( AMA 1). Previously vaccinated volunteers show boosting of pre‐existing antigen‐specific memory B ‐cell (m BC ) responses following CHMI . In contrast, unvaccinated malaria‐naive control volunteers developed an m BC response against MSP 1 but not AMA 1. Serum I g G correlated with the m BC response after booster vaccination but this relationship was less well maintained following CHMI . A significant reduction in peripheral MSP 1‐specific m BC was observed at the point of diagnosis of blood‐stage infection. This was coincident with a reduction in peripheral blood B ‐cell subsets expressing CXCR 3 and elevated serum levels of interferon‐ γ and CXCL 9, suggesting migration away from the periphery. These CHMI data confirm that m BC and antibody responses can be induced and boosted by blood‐stage parasite exposure, in support of epidemiological studies on low‐level parasite exposure.