Acquisition and decay of IgM and IgG responses to merozoite antigens after Plasmodium falciparum malaria in Ghanaian children

Abstract

Developing a vaccine against Plasmodium falciparum malaria has been challenging, primarily due to high levels of antigen polymorphism and a complex parasite lifecycle. Immunization with the P. falciparum merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 has been shown to give rise to growth inhibitory and synergistic antisera. Therefore, these five merozoite proteins are considered to be promising candidates for a second-generation multivalent malaria vaccine. Nevertheless, little is known about IgG and IgM responses to these antigens in populations that are naturally exposed to P. falciparum. In this study, serum samples from clinically immune adults and malaria exposed children from Ghana were studied to compare levels of IgG and IgM specific for PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5. All five antigens were found to be specifically recognized by both IgM and IgG in serum from clinically immune adults and from children with malaria. Longitudinal analysis of the latter group showed an early, transient IgM response that was followed by IgG, which peaked 14 days after the initial diagnosis. IgG levels and parasitemia did not correlate, whereas parasitemia was weakly positively correlated with IgM levels. These findings show that IgG and IgM specific for merozoite antigens PfMSRP5, PfSERA9, PfRAMA, PfCyRPA and PfRH5 are high in children during P. falciparum malaria, but that the IgM induction and decline occurs earlier in infection than that of IgG.

Age dependent changes in circulating Tfh cells influence the development of functional antibodies to malaria in children.

“…There was also some boosting to non-blood stage antigens, with increased OPA antibodies to both CSP and Pfs230 during infection. IgM antibodies were not increased to any antigens in currently infected children, in contrast with previous findings by ourselves and others (Boyle et al, 2019;Walker et al, 2020).…”

Naturally acquired antibody kinetics against Plasmodium vivax antigens in people from a low malaria transmission region in western Thailand

“…In contrast, we found that hyper-immune adults from PNG (used as the positive control pool) had similar levels of IgG1 and IgG3 to multiple P. vivax proteins, and that the level of IgG3 was higher compared to that of the Thai symptomatic patients to most proteins (Figure S3). Naturally acquired antigen-specific IgM responses are longer-lived than total IgG following symptomatic P. vivax infections Whilst IgM responses are traditionally thought to be transient following infections, more recent evidence has suggested they can be long-lived or follow a similar kinetic to IgG, at least in the context of malaria [44,45], though this is likely dependent on the antigen assessed and transmission setting [46]. We first assessed IgM immunogenicity at 1-week post-infection in the symptomatic cohort and classified 15 antigens as IgMpositive (more than 2 SD above baseline), including both IgG-immunogenic (n=8) and non-IgG-immunogenic (n=7) antigens (Figure S4).…”

Strain-Dependent Inhibition of Erythrocyte Invasion by Monoclonal Antibodies Against Plasmodium falciparum CyRPA

“…PfCyRPA is a 43 kDa protein with only one single-nucleotide polymorphism (SNP), R339S, above 5% prevalence (14). The protein is fundamental for erythrocyte invasion as conditional knockdown causes the loss of invasion activity (11,15) and the protein has low sero-reactivity from natural exposure (16)(17)(18).…”