Malaria infections due to Plasmodium vivax are a major challenge for elimination in the Asia-Pacific region. Novels tools for surveillance and prevention that specifically target P. vivax are required. Improving our understanding of naturally acquired immune responses induced following P. vivax infections could enable novel strategies to be implemented, including the use of antibodies for serological surveillance and/or identifying antibodies as correlates of immunity. In this study we aimed to characterise the P. vivax-specific functional complement-fixing antibody response in individuals following clinical P. vivax infections.
We developed a novel multiplexed assay that can measure complement-fixing antibodies to a panel of 25 P. vivax proteins simultaneously. We applied this assay to a cohort of 34 P. vivax patients in Thailand, with intense follow up every 2-4 weeks for 9-months. At the time of P. vivax infection, we identified complement-fixing antibodies above background to all 25 proteins in at least some individuals. There was significant variability in the level of complement-fixing antibodies between individuals and against different P. vivax proteins. Despite the variability, there was a clear peak in the complement-fixing antibody response at the time of infection, which declined to baseline by 4 months post infection. In comparison to total IgG antibody responses, the complement-fixing response was short-lived. At the peak of the IgG antibody response, there was a statistically significant correlation between the level of total IgG antibodies and complement-fixing antibodies for 21 of 24 P. vivax proteins.
Given the short-lived nature of complement-fixing antibodies in this cohort, we are assessing their ability to act as markers of exposure to recent P. vivax infections. Given complement-fixing antibodies are better correlated with protection from clinical malaria in the context of P. falciparum infections, we are also assessing the association of complement-fixing antibodies to these proteins with protection from subsequent clinical infections.