Immune requirements for protection during secondary Plasmodium infection

Abstract

Abstract Malaria, caused by Plasmodium parasites, is one of the top infectious killers of children worldwide. Decades-long efforts to develop a vaccine have so far resulted in a single licensed vaccine with modest efficacy; a better understanding of naturally acquired protective mechanisms could lead to improved vaccine design. Previous work in humans and animal models has identified roles for B cells, CD4+ T cells, and phagocytes in clearance of a primary or established infection, but we still lack a clear understanding of which immune factors are required to restrict Plasmodium from replicating in previously exposed, immune hosts. In this study, we tested whether various immune effectors were required to limit parasitemia in immune mice experiencing a second infection with the rodent-adapted strain P. chabaudi. We found that phagocytes and circulating antibody were critical for homologous secondary protection, whereas B cells were dispensable. CD4+ T cells were also required for full protection, indicating that they continue to play an important role even after antibody responses are established. We speculate that memory B cells may be important for protection from heterologous parasite strains, a hypothesis that remains to be tested. This study underlines the need for a vaccine to induce multiple immune axes in order to confer protective immunity from malaria.