Identifying Plasmodium P36 and P52 antigens for coadministration with circumsporozoite protein to enhance vaccine efficacy

Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from the inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP. Co-administration of P36 and/or P52 with CSP achieved 80-100% sterile protection in mice, compared to only 7-30% protection for each individual antigen. P36 and P52 vaccination induced murine CD4⁺ and CD8⁺ T cell responses, but not antibody responses. This study adds P36 and P52 as promising vaccine antigens that may enhance the protection achieved by CSP vaccination.