Malaria infections due to Plasmodium vivax are a major challenge for elimination in the Asia-Pacific region. Improved surveillance tools appropriate for use in low transmission settings are required. Improving our understanding of naturally acquired immune responses induced following P. vivax infections could enable novel strategies to be implemented. In this study we aimed to characterise the P. vivax-specific antibody response in individuals from endemic areas by assessing the acquisition and decay of total IgG, IgG subclass, IgM and functional antibodies.
Using a panel of 60 P. vivax proteins, we identified a bi-phasic pattern of IgG antibody decay over 9 months, following a peak 1-2 weeks after clinical P. vivax infection in Thai patients (n=34). In these individuals with limited past exposure, IgG1 was the dominant subclass and followed similar kinetics to total IgG. We observed that IgM responses are long-lived in these Thai patients. To assess functional antibody responses, we have developed and validated a novel multiplexed assay to measure the interaction between P. vivax-specific IgG and complement (C1q). We are currently measuring the presence and decay of C1q-fixing antibodies in the same cohort of Thai patients.
We tested the use of antibody responses to all 60 proteins for classifying individuals as recently exposed to P. vivax parasites or not. Using total IgG responses to a panel of 8 P. vivax proteins, we could accurately classify recent exposure with > 80% sensitivity and specificity using large yearlong observational cohort studies in Thailand (n=829), Brazil (n=928) and the Solomon Islands (n=754). These serological markers of recent exposure can enable efficient targeting of limited resources for malaria elimination, and highlight the value in increasing our understanding of naturally acquired immune responses to malaria.