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.
Highlights
PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles
The PvMSP1 experimentally defined promiscuous T cell epitopes were arrayed in tandem and genetically fused to an extended PvMSP119 that includes two predicted T helper epitopes present in MSP133 (Fig. 1A,B)
When the SDS-PAGE was performed under reducing conditions, a shift in the mobility was observed for both PvRMC-MSP1 and PvMSP119, indicating that the disulfide bonds present in PvMSP119 that are critical for biological activity are preserved in PvRMC-MSP1 (Supplementary Figure S2)
Summary
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. 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. The PvRMC-MSP1 protein was 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. MSP133 specific CD4+T cells have shown to be involved in protection in the murine model via IFN-γproduction, and induction of cytophilic antibodies[15,16] These features have been confirmed in humans as CD4+T cells able to recognize blood stage antigens have been linked to protection[17]
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