Abstract
BackgroundThe ability of a malaria antigen to induce effective, long-lasting immune responses is important for the development of a protective malaria vaccine. Plasmodium vivax merozoite surface protein-8 (PvMSP8) has been shown to be immunogenic in natural P. vivax infections and produces both cell-mediated and antibody-mediated immunity. Thus, PvMSP8 has been proposed as a vaccine candidate following fusion with other merozoite antigens in blood stage vaccine design. Here, the long-term responses of antibodies and memory B cells (MBCs) specific to PvMSP8 in individuals were monitored in a longitudinal cohort study.MethodsBoth cross-sectional surveys and cohort studies were utilized to explore the persistence of antibody and MBC responses to PvMSP8. Antibody titers were detected in individuals with acute disease and those who recovered from an infection for 4 years. The dominant peptide epitope of PvMSP8 recognized by naturally acquired antibodies was examined to observe the durability of the post-infection antibody response. PvMSP8-specific MBCs were also in subjects 4 years post-infection using an enzyme-linked immunospot assay.ResultsThe prevalence of antibodies to PvMSP8 was high during and after infection. The antibody levels in individual responders were monitored for up to 12 months post-infection and showed that most patients maintained their seropositive response. Interestingly, the anti-PvMSP8 antibody responses stably persisted in some patients who had recovered from an infection for 4 years. Positive PvMSP8-specific MBCs were also detected at 4 years post-infection. However, analysis in these individuals showed no correlation with the presence or titer of circulating antibody.ConclusionPvMSP8 had the ability to induce a long-term humoral immune response. The antibodies and MBCs specific for this antigen developed and persisted in subjects who acquired a natural P. vivax infection. Inclusion of the PvMSP8 antigen in blood stage vaccine design should be considered.
Highlights
The ability of a malaria antigen to induce effective, long-lasting immune responses is important for the development of a protective malaria vaccine
Malaria vaccines are generally classified based on their target within the parasite lifecycle: (i) a pre-erythrocytic vaccine aims to prevent blood stage infections, (ii) a blood stage vaccine aims to clear parasitaemia and prevent clinical disease, and (iii) a transmission-blocking vaccine aims to prevent the infection of mosquitoes and interrupt the malaria transmission cycle [1]
Prevalence of anti‐IgG Plasmodium vivax merozoite surface protein-8 (PvMSP8) antibodies through 4 years post‐infection Sixteen patients in the sub-cohort 1 study were analysed to detect anti-PvMSP8 antibody levels and determine the longevity of anti-PvMSP8 responses after infection (Table 2)
Summary
The ability of a malaria antigen to induce effective, long-lasting immune responses is important for the development of a protective malaria vaccine. The leading vaccine candidate against the blood stage of Plasmodium vivax is Duffy binding protein region II (DBPII), the only candidate antigen that has currently reached clinical trials [2]. The increasing recognition of P. vivax infections in Duffy-negative individuals suggests that there is an alternative pathway for the parasites to invade red blood cells. Together, this suggests that a combination of antigens would enhance the efficacy of a vivax malaria vaccine and more likely lead to broadly protective immune responses
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