A malaria vaccine candidate based on a hepatitis B virus core platform

• <i>Objective:</i> The recent success of a <i>Plasmodium falciparum</i> malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes. <i>Methods:</i> Well-characterized CSP-specific neutralizing B cell epitopes and a ‘universal’ T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. <i>Results:</i> The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 10⁶ titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. <i>Conclusion:</i> These characteristics suggest that V12.PF3.1 represents an efficient and economical <i>P. falciparum</i> vaccine candidate for use separately or in combination with other formulations.

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