Tailoring a P. vivax vaccine to enhance efficacy through a combination of a CSP Virus-Like Particle Rv21 and TRAP viral vectors.

Vivax malaria remains one of the most serious and neglected tropical diseases with 132-391 million clinical cases per year and 2.5 billion at risk of infection. A vaccine against Plasmodium vivax could have more impact than any other intervention and the use of of a vaccine targeting multiple antigens may result in higher efficacy against sporozoite infection than targeting a single antigen. Here two leading P. vivax pre-erythrocytic vaccine candidate antigens, the circumsporozoite protein (PvCSP) and the Thrombospondin Related Adhesion Protein (PvTRAP) were delivered as a combined vaccine. This strategy provided a dose sparing effect with 100% sterile protection in mice using doses that individually conferred low or no protection like the unadjuvanted antigens PvTRAP (0%) and PvCSP (50%), thus reaching similar protection to adjuvanted components. Efficacy against malaria infection was assessed using a new mouse challenge model consisting of a double transgenic P. berghei parasite simultaneously expressing PvCSP and PvTRAP used in mice immunized with the Virus-Like Particle (VLP) Rv21 previously reported to induce high efficacy in mice using Matrix M adjuvant, while PvTRAP was concomitantly administered in chimpanzee adenovirus and MVA vectors (vvTRAP) to support effective induction of T cells. We examined immunity elicited by these vaccines in the context of two adjuvants approved for human use (AddaVax and Matrix M). Matrix M supported the highest anti-PvCSP antibody titres when combined with the Rv21 and interestingly, mixing PvCSP Rv21 and PvTRAP viral vectors enhanced immunity to malaria over single vaccines.