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

Rodolfo F Marques,Alba Marina Gimenez,Mariana R Dominguez,Ii-Sei Watanabe,Janaina T Novais,Eduardo L V Silveira,Diego P Cury,Eduardo Aliprandini,Rogerio Amino,Irene S Soares

doi:10.3390/vaccines8020190

Abstract

Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax 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 P. vivax circumsporozoite protein (PvCSP—All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (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 P. vivax-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To elicit stronger humoral and cellular responses, Pichia pastoris 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-CSPCT 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 P. vivax malaria.

Highlights

Plasmodium vivax is the second most prevalent species causing malaria in the world, occurring mainly in South and Southeast Asia, the Western Pacific, the Eastern Mediterranean, Central America, and South America [1]
Public health experts have considered the development of a malaria vaccine to be a research priority [4], clinical research for P. vivax vaccines has been mostly neglected
The gene sequences encoding recombinant P. vivax circumsporozoite (PvCSP) proteins nucleocapsid-like particles (NLPs)-CSPCT and NLP-CSPR were synthesized using codon optimization for expression in P. pastoris (GenScript, Piscataway, NJ, USA). Both proteins contained the three variant tandem repeats domains of PvCSP [22] fused with the mumps virus nucleocapsid protein (UniProtKB/Swiss-Prot: AFO62160) sequence

Summary

Introduction

Plasmodium vivax is the second most prevalent species causing malaria in the world, occurring mainly in South and Southeast Asia, the Western Pacific, the Eastern Mediterranean, Central America, and South America [1]. Recent data estimate that 7.5 million malaria cases are caused by P. vivax. The mortality induced by P. vivax infection is considered to be very low when compared to P. falciparum infection. P. vivax-derived morbidity has significantly increased during the last few years due to the development of chloroquine resistance by the parasite [2]. Public health experts have considered the development of a malaria vaccine to be a research priority [4], clinical research for P. vivax vaccines has been mostly neglected. Only a few trials for vaccines against P. vivax malaria have been performed [5]

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