Analysis of naturally acquired immune responses against the Plasmodium falciparummalaria vaccine candidate PF3D7_1136200

Abstract

Abstract Humoral immunity is critical for protection against Plasmodium falciparum malaria. In endemic areas, individuals acquire protective immunity against malaria through repeated exposure to P. falciparum parasites. Understanding these naturally acquired immune responses would be highly informative for the development of improved vaccination strategies against malaria. Antibody responses against the uncharacterized protein PF3D7_1136200 correlate with protection from malaria, however, the development of these antibody responses over time and their role in protecting against malaria remain unknown. Here, we compared PF3D7_1136200-specific antibody and B cell responses to that of other P. falciparum antigens in Ugandan individuals with different immune status: immune adults (n=24) and children with high (n=10) or low (n=8) susceptibility to malaria. In all groups, serum antibody reactivity against MSP1, MSP3, AMA1, VFT, Pf41, and Pf113 was dominated by IgG. In contrast, serum IgG antibody reactivity against PF3D7_1136200 was much lower, while IgM reactivity was at a similar or higher level compared to these antigens. In line with the low serum IgG reactivity against PF3D7_1136200 among adults, we exclusively observed IgM +memory B cells (MBCs) against PF3D7_1136200, while IgG +MBCs were more abundant than IgM +MBCs for all other antigens. These results indicate that PF3D7_1136200 has a low antigenic profile, similar to that of other favorable P. falciparum vaccine candidates, and suggest potential shielding of antigen from the host immune system. Together with the genetic conservation of PF3D7_1136200, these characteristics highlight that Pf3D7_1136200 has potential as a novel vaccine candidate against malaria. Supported by grants from NIH (R01 AI153425, P30 CA054174-20)