Defining antibody kinetics and longevity to 40 Plasmodium vivax antigens in individuals from western Thailand

Plasmodium vivax is the dominant Plasmodium spp. in low-transmission regions outside of Africa. Such regions often feature a high proportion of asymptomatic patients with sub-microscopic parasitaemia, with many of these infections thought to be caused by frequent relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. However, previous work has failed to address such antibody responses to P. vivax, particularly in low-transmission regions. We have recently conducted a study in western Thailand to monitor antibody kinetics for 9 months following symptomatic P. vivax infections, in the absence of any recurrent infections during this time frame. Using a high-throughput system (AlphaScreen), we assessed IgG levels to more than 300 crude P. vivax proteins at 4 time points: enrolment, 3, 6 and 9 months; and identified several P. vivax-derived antigens that induce antibody responses with varying decay profiles. We have validated the high-throughput screening results using a different approach, Luminex, with highly purified proteins, to measure antibody levels at an increased number of time points to a sub-set of 40 antigens, in an attempt to obtain antibody decay profiles of greater resolution. We found that the decay profiles captured using the two approaches are correlated, with antigens with short-lived antibody kinetic profiles better correlated than those inducing a long-lived response. Additionally, it is observed that the antibody responses induced by some antigens are below a seropositivity cut-off, most of which are those of long-lived profiles. For most antigensinvestigated, an increase in antibody level was observed within the first week following detection of symptomatic infection, followed by an exponential decay of different rates. Mathematical modelling of longitudinal data on antibody responses allows characterisation of the decay profiles as exponential or bi-phasic exponential, and investigation of how variation in these antigen-specific antibody kinetic profiles depends on avidity, IgG subclass, IgM. Upon completion of this work, we will have gained invaluable insights into the development of naturally acquired immunity to P. vivax and the potential use of serology as a new surveillance tool for eliminating malaria.