PD-1 deficiency enhances humoral immunity of malaria infection treatment vaccine.

Malaria infection treatment vaccine (ITV) is a promising strategy to induce homologous and heterologous protective immunity against the blood stage of the parasite. However, the underlying mechanism of protection remains largely unknown. Here, we found that a malaria-specific antibody (Ab) could mediate the protective immunity of ITV-immunized mice. Interestingly, PD-1 deficiency greatly elevated the levels of both malaria-specific total IgG and subclass IgG2a and enhanced the protective efficacy of ITV-immunized mice against the blood-stage challenge. A serum adoptive-transfer assay demonstrated that the increased Ab level contributed to the enhanced protective efficacy of the immunized PD-1-deficient mice. Further study showed that PD-1 deficiency could also promote the expansion of germinal center (GC) B cells and malaria parasite-specific TFH cells in the spleens of ITV-immunized mice. These results suggest that PD-1 deficiency improves the protective efficacy of ITV-immunized mice by promoting the generation of malaria parasite-specific Ab and the expansion of GC B cells. The results of this study provide new evidence to support the negative function of PD-1 on humoral immunity and will guide the design of a more effective malaria vaccine.