A chimeric protein-based malaria vaccine candidate induces robust T cell responses against Plasmodium vivax MSP119

Abstract

The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119. This vaccine candidate preserved structural elements of the native PvMSP119 and elicited cytophilic antibody responses, and CD4+ and CD8+ T cells capable of recognizing PvMSP119. Although CD8+ T cells that recognize blood stage antigens have been reported to control blood infection, CD8+ T cell responses induced by P. falciparum or P. vivax vaccine candidates based on MSP119 have not been reported. To our knowledge, this is the first time a protein based subunit vaccine has been able to induce CD8+ T cell against PvMSP119. The PvRMC-MSP1 protein was also recognized by naturally acquired antibodies from individuals living in malaria endemic areas with an antibody profile associated with protection from infection. These features make PvRMC-MSP1 a promising vaccine candidate.

Exposure to Plasmodium vivax is associated with the increased expression of exhaustion markers on γδ T lymphocytes

“…Malaria caused by Plasmodium vivax is relatively common, accounting for 15 million annual clinical cases and leaving 2.5 billion people at risk of infection . The clinical manifestations associated with P. vivax range from uncomplicated febrile illness to severe illness, such as acute kidney injury, acute lung injury, coma and death.…”

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Malaria caused by Plasmodium vivax is relatively common, accounting for 15 million annual clinical cases and leaving 2.5 billion people at risk of infection. 1,2 The clinical manifestations associated with P. vivax range from uncomplicated febrile illness to severe illness, such as acute kidney injury, acute lung injury, coma and death. P. vivax is capable of provoking fever at a lower level of parasitaemia, with a pyrogenic density of 180 parasites per μL compared to 1000 parasites per μL for P. falciparum.

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Protective Immunity in Mice Immunized With P. vivax MSP119-Based Formulations and Challenged With P. berghei Expressing PvMSP119

“…Many vaccine formulations based on the PvMSP1 19 or PvMSP1 42 sequences have been developed and had their immunogenicity in mice, and sometimes in non-human primates, studied (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). In the last years, we developed recombinant proteins based on the sequence of the PvMSP1 19 formulated in different adjuvant systems.…”

Natural Infections With Different Plasmodium Species Induce Antibodies Reactive to A Chimeric Plasmodium Vivax Recombinant Protein

“…Our group has previously designed, cloned, and expressed a chimeric P. vivax MSP1 protein (designated PvRMC-MSP1) for the primary purposes of malaria vaccine studies. This chimeric protein contains an extended version of PvMSP1 19 containing two T helper epitopes present in the PvMSP1 33 fragment of the native protein, ve promiscuous T cell epitopes (capable of binding multiple MHC Class II alleles) arrayed in tandem, and a C-terminal (NANP) 6 a nity tag derived from the central repeat region of the P. falciparum CSP (27). The T cell epitopes in PvRMC-MSP1 represent different regions of PvMSP1 able to bind to several MHC class II alleles, with two epitopes also functioning as B cell epitopes (28).…”

“…The T cell epitopes in PvRMC-MSP1 represent different regions of PvMSP1 able to bind to several MHC class II alleles, with two epitopes also functioning as B cell epitopes (28). We have previously reported that PvRMC-MSP1 was recognized by antibodies from individuals living in malaria-endemic areas of Brazil with no indication of genetic restriction based on HLA-DRB1 and HLA-DQB1* allele frequencies (27). Due to the evidence that PvRMC-MSP1 can capture IgG from naturally exposed individuals, we evaluated the ability of PvRMC-MSP1 to induce antibodies that bind to nonvivax-speci c antigenic targets and the ability of PvRMC-MSP1 to capture naturally acquired IgG antibodies from exposed individuals with known infection status from all four human Plasmodium species.…”