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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.

Original publication




Journal article


Infection and immunity

Publication Date



The Jenner Institute, University of Oxford, Old Road Campus Research Building. Roosevelt Drive, Oxford, OX3 7DQ, UK.