Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein

Abstract

<i>Plasmodium vivax</i> is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although <i>Plasmodium falciparum</i> causes the majority of deaths, <i>P. vivax</i> can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the <i>P. vivax</i> circumsporozoite protein (PvCSP-All epitopes) showed partial protection in mice after a challenge with the hybrid <i>Plasmodium berghei</i> (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and <i>P. vivax</i>-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSP_R) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSP_CT). To elicit stronger humoral and cellular responses, <i>Pichia pastoris</i> yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSP_CT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against <i>P. vivax</i> malaria.