A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles

Alba Marina Gimenez,Irene S Soares,Chris J Janse,Young Chan Kim,César López-Camacho,Ahmed M Salman,Arturo Reyes-Sandoval,Kate Harrison,Rodolfo F Marques

doi:10.1038/s41598-021-96986-1

Abstract

Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Among the species of Plasmodium causing human malaria, P. vivax is the second most prevalent and the most geographically widespread species. A major target of a pre-erythrocytic vaccine is the P. vivax circumsporozoite protein (PvCSP). In previous studies, we fused two recombinant proteins representing three allelic variants of PvCSP (VK210, VK247 and P. vivax-like) to the mumps virus nucleocapsid protein to enhance immune responses against PvCSP. The objective of the present study was to evaluate the protective efficacy of these recombinants in mice challenged with transgenic P. berghei parasites expressing PvCSP allelic variants. Formulations containing Poly (I:C) or Montanide ISA720 as adjuvants elicited high and long-lasting IgG antibody titers specific to each PvCSP allelic variant. Immunized mice were challenged with two existing chimeric P. berghei parasite lines expressing PvCSP-VK210 and PvCSP-VK247. We also developed a novel chimeric line expressing the third allelic variant, PvCSP-P. vivax-like, as a new murine immunization-challenge model. Our formulations conferred partial protection (significant delay in the time to reach 1% parasitemia) against challenge with the three chimeric parasites. Our results provide insights into the development of a vaccine targeting multiple strains of P. vivax.

Highlights

Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide
The development of an effective vaccine would be an important tool against malaria, as it would provide a costeffective form of prevention and would help circumvent adaptive strategies both from the vector and parasite
Since a significant proportion of sporozoites released in the challenge were prevented from causing an infection, our formulation could hypothetically contribute to the reduction in cases of relapse, as it would prevent the formation of new hypnozoites in the liver[49]

Summary

Introduction

Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Human malaria is caused by five different etiological agents, all belonging to the phylum Apicomplexa and the genus Plasmodium: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. The latter is a non-human primate (NHP) parasite that causes infections in humans, including severe malaria[1]. A third variant from a parasite that causes P. vivax malaria in humans, called Plasmodium vivax-like, expresses CSP with APGANQ(E/G)GAA repeats (hereafter named PvCSP-P. vivax-like) and was described in endemic regions of Papua New Guinea, Brazil, Indonesia and Madagascar[11]. Other Plasmodium specie that commonly infects NHP and causes zoonotic P. vivax malaria in humans is P. simium, which shares high genetic identity with P. vivax[20] and their two main CSP variants (VK210 and VK247) are identical[21]. A universal vaccine against all types of P. vivax malaria should include the VK210 and VK247 P. vivax variants and the P. vivax-like variant

Objectives

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Conclusion