A multivalent Plasmodium falciparum circumsporozoite protein-based nanoparticle malaria vaccine elicits a robust and durable antibody response against the junctional epitope and the major repeats

Plasmodium falciparum (Pf) malaria continues to cause considerable morbidity and mortality worldwide. The circumsporozoite protein (CSP) is a particularly attractive candidate for designing vaccines that target sporozoites-the first vertebrate stage in a malaria infection. Current PfCSP-based vaccines, however, do not include epitopes that have recently been shown to be the target of potent neutralizing antibodies. We report the design of a SpyCatcher-mi3-nanoparticle-based vaccine presenting multiple copies of a chimeric PfCSP (cPfCSP) antigen that incorporates these important T1/junctional epitopes as well as a reduced number of (NANP)(n) repeats. cPfCSP-SpyCatcher-mi3 was immunogenic in mice eliciting high and durable IgG antibody levels as well as a balanced antibody response against the T1/junctional region and the (NANP)(n) repeats. Notably, the antibody concentration elicited by immunization was significantly greater than the reported protective threshold defined in a murine challenge model. Refocusing the immune response toward functionally relevant subdominant epitopes to induce a more balanced and durable immune response may enable the design of a more effective second generation PfCSP-based vaccine.

Automated summary

A vaccine based on SpyCatcher-mi3 nanoparticles presenting a chimeric PfCSP antigen was designed to target the malaria parasite Plasmodium falciparum (Pf). This vaccine incorporates recently identified T1/junctional epitopes and reduces the number of (NANP)(n) repeats. Immunization with this vaccine in mice resulted in high and durable IgG antibody levels and a balanced antibody response against T1/junctional epitopes and (NANP)(n) repeats. Refocusing the immune response towards functionally relevant epitopes may lead to a more effective second generation PfCSP-based vaccine.