Evaluation of immunogenicity and efficacy of a Plasmodium vivax nanoparticle vaccine in mice.

BACKGROUND

Plasmodium vivax malaria is an increasing global health threat and the second leading cause of malaria globally. An efficacious vaccine aimed at preventing disease and transmission would greatly facilitate malaria elimination. The P. vivax circumsporozoite protein (PvCSP) is considered a leading pre-erythrocytic stage vaccine target. While P. falciparum malaria vaccines currently in clinical use have CSP as the critical component, their limited efficacy and the need for multiple doses continue to pose challenges for malaria vaccines. This study evaluated a novel customized size-tuned nanoparticle production and conjugation protocol co-displaying PvCSP with a TLR agonist as a vaccine platform to induce sporozoite-neutralizing antibodies to prevent sporozoite infection of hepatocytes.

METHODS

The immunogenicity and efficacy of a P. vivax CSP nanoparticle vaccine (NPV) were evaluated in BALB/c mice. Vaccine-induced antibody titers were assessed by standard ELISA, and their ability to inhibit sporozoite infection of hepatocytes was tested using transgenic P. berghei sporozoites expressing P. vivax CSP.

RESULTS

The CSP-NPV elicited high-titer anti-CSP antibodies that significantly inhibited hepatocyte infection by transgenic P. berghei sporozoites expressing P. vivax CSP in vitro and partially protected mice following in vivo sporozoite challenge.

CONCLUSIONS

These data validate NPVs as a suitable CSP vaccine delivery platform to prevent sporozoite infection. Its versatility makes it suitable for testing other PE vaccine antigens and adjuvants for the potential development of a multivalent vivax malaria vaccine.