Researchers registered 348 participants in Haiti's Malaria Zero Program in Grand Anse to evaluate immune responses to salivary peptides from Nyssorhynchus and Anopheles subgenera. The study assessed IgG antibody levels against Peroxi-P3, Apy2, and gSG6-P1 to characterize human-vector-parasite exposure dynamics in this low-transmission area.
Significantly elevated IgG responses were observed for Peroxi-P3 compared to Apy2 and gSG6-P1, with a p-value less than 0.001. Immune responses to Peroxi-P3 and gSG6-P1 differed significantly between participants aged 18 years or younger and those older than 18 years (p = 0.004 and p = 0.002, respectively). No sex-based differences were observed in immune responses to any peptide.
A greater number of significant positive associations were found between gSG6-P1 and Plasmodium antigens than with any other salivary peptide. Participants who owned a single household animal species exhibited a marked reduction in IgG responses to Apy2 and Peroxi-P3 compared to those with two or more species or no animals; gSG6-P1 responses were not affected. Spatial analysis revealed heterogeneous geographic overlap of high antibody responses among the peptides, alongside clusters of low responses to Peroxi-P3 and Apy2.
No adverse events, serious adverse events, discontinuations, or tolerability data were reported. Key limitations include the observational design, which precludes causal inference, and the lack of reported follow-up or specific p-values for some comparisons. These data provide additional context on the utility of anopheline salivary peptides for characterizing exposure dynamics in low-transmission settings.
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Anopheles albimanus (Nyssorhynchus) is featured as the main malaria vector on Hispaniola. However, five other Anopheles species have been reported circulating in the area; four of them belonging to the subgenus Anopheles (An. crucians, An. grabhamii, An. pseudopunctipennis, and An. vestitipennis) and another one to the Nyssorhynchus subgenus (An. argyritarsis). Previous studies on mosquitoes in the genus Anopheles have identified and characterized peptides from immunogenic salivary proteins, with several of these peptides being unique to the Nyssorhynchus and Anopheles subgenera. This underscores their potential use as biomarkers for differentiating exposure to Anopheles mosquitoes in both the Old World and New World. Since both Nyssorhynchus and Anopheles subgenera have been reported in Haiti, a series of ELISAs were conducted to quantify IgG antibody titers against three published antigenic anopheline salivary peptides (gSG6-P1, Peroxi-P3, and Apy-2) in 348 participants registered in Haitis multi-partner/multidisciplinary Malaria Zero Program. This study aimed to evaluate the intensity of human-vector contact with Anopheles from both subgenera in Grand Anse, Haiti. In addition, the study measured antibodies against a panel of Plasmodium falciparum antigens to determine any association between anti-parasite and anti-peptide antibodies. Significantly elevated IgG responses to Peroxi-P3 in comparison to Apy2 and gSG6-P1 in the total study population (p < 0.001) were observed. Additionally, immune responses to Peroxi-P3 and gSG6-P1 differed significantly between [≤]18-year-olds and >18-year-olds (p = 0.004 and p = 0.002), whereas no sex-based differences were observed for any peptide. Correlation analyses observed a greater number of significant positive associations in immune response between gSG6-P1 and Plasmodium antigens than any other salivary peptide, an occurrence which was more pronounced in [≤]18-year-olds than >18-year-olds. A marked reduction in IgG responses to Apy2 and Peroxi-P3, but not gSG6-P1, among participants who kept a single household animal species compared with those who owned two or more species or those who did not have household animals was also demonstrated. Spatial analysis revealed heterogenous geographic overlap of high antibody responses among Peroxi-P3, Apy2, and gSG6-P1, alongside geographically overlapping clusters of low antibody responses to Peroxi-P3 and Apy2. These results provide additional data on the utility of anopheline salivary peptides to characterize human-vector-parasite exposure dynamics in low-transmission areas, such as Haiti.
