Abstract
Background Plasmodium vivax is the most geographically widespread human malaria parasite. Cohort studies in Papua New Guinea have identified a rapid onset of immunity against vivax-malaria in children living in highly endemic areas. Although numerous P. vivax merozoite antigens are targets of naturally acquired antibodies, the role of many of these antibodies in protective immunity is yet unknown.Methodology/Principal FindingsIn a cohort of children aged 1–3 years, antibodies to different regions of Merozoite Surface Protein 3α (PvMSP3α) and Merozoite Surface Protein 9 (PvMSP9) were measured and related to prospective risk of P. vivax malaria during 16 months of active follow-up. Overall, there was a low prevalence of antibodies to PvMSP3α and PvMSP9 proteins (9–65%). Antibodies to the PvMSP3α N-terminal, Block I and Block II regions increased significantly with age while antibodies to the PvMSP3α Block I and PvMSP9 N-terminal regions were positively associated with concurrent P. vivax infection. Independent of exposure (defined as the number of genetically distinct blood-stage infection acquired over time (molFOB)) and age, antibodies specific to both PvMSP3α Block II (adjusted incidence ratio (aIRR) = 0.59, p = 0.011) and PvMSP9 N-terminus (aIRR = 0.68, p = 0.035) were associated with protection against clinical P. vivax malaria. This protection was most pronounced against high-density infections. For PvMSP3α Block II, the effect was stronger with higher levels of antibodies.ConclusionsThese results indicate that PvMSP3α Block II and PvMSP9 N-terminus should be further investigated for their potential as P. vivax vaccine antigens. Controlling for molFOB assures that the observed associations are not confounded by individual differences in exposure.
Highlights
Most malaria vaccine research and development has been focused on Plasmodium falciparum
These results indicate that PvMSP3a Block II and PvMSP9 N-terminus should be further investigated for their potential as P. vivax vaccine antigens
In a cohort of 183 children aged 1–3 years, we show that the presence of antibodies to Merozoite Surface Protein 3a (PvMSP3a) and Merozoite Surface Protein 9 (PvMSP9) are associated with a significant reduction in the burden P. vivax malaria
Summary
Most malaria vaccine research and development has been focused on Plasmodium falciparum. P. vivax is the most geographically widespread malaria parasite with up to 2.5 billion people at risk and an estimated 80–300 million clinical cases every year [2]. It is not the benign parasite it was long assumed to be; while severe manifestations are less common [3], there is a spectrum of severe disease associated with P. vivax infection that in many ways resembles that seen with P. falciparum [4]. Plasmodium vivax is the most geographically widespread human malaria parasite. Numerous P. vivax merozoite antigens are targets of naturally acquired antibodies, the role of many of these antibodies in protective immunity is yet unknown
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