A malaria serological map indicating the intersection between parasite antigenic diversity and host antibody repertoires

Abstract

A malaria vaccine targeting Plasmodium falciparum remains a strategic goal for malaria control. If a polyvalent vaccine is to be developed, its subunits would probably be chosen based on immunogenicity (concentration of elicited antibodies) and associations of selected antigens with protection. We propose an additional possible selection criterion for the inclusion of subunit antigens; that is, coordination between elicited antibodies. For the quantitative estimation of this coordination, we developed a malaria serological map (MSM). Construction of the MSM was based on three categories of variables: (i) malaria antigens, (ii) total IgG and IgG subclasses, (iii) different sources of plasma. To validate the MSM, in this study, we used four malaria antigens (AMA1, MSP2-3D7, MSP2-FC27 and Pf332-C231) and re-grouped the plasma samples into five pairs of subsets based on age, gender, residence, HbAS and malaria morbidity in 9 years. The plasma total IgG and IgG subclasses to the test antigens were measured, and the whole material was used for the MSM construction. Most of the variables in the MSM were previously tested and their associations with malaria morbidity are known. The coordination of response to each antigens pair in the MSM was quantified as the correlation rate (CR = overall number of significant correlations/total number of correlations × 100 %). Unexpectedly, the results showed that low CRs were mostly associated with variables linked with malaria protection and the antigen eliciting the least CRs was the one associated with protection. The MSM is, thus, of potential value for vaccine design and understanding of malaria natural immunity.

Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3

“…Indeed, the IgG1 and IgG3 sub-classes have been shown to play a role in anti-merozoite responses [ 23 , 24 ]. Children in areas of high P. falciparum transmission are known to develop a strong antibody response to PfEMP1 [ 25 , 26 ]. However, in this study, the anti-PfEMP1 antibody response was weak and did not correlate with reduced risk of clinical disease.…”

Trade-offs in antibody repertoires to complex antigens

“…For some antigens, the majority of induced B cells within and across hosts target the same epitope, indicating consistent patterns of immunodominance [ 11 ]. For other antigens, evolved B-cell populations show adaptation to different epitopes [ 12 – 14 ]. These differences may arise from variability in the accessibility of binding sites on the antigen, the genetic diversity of a host's naive B-cell population, stochastic founding events in GCs, genetic predisposition mediated by helper T cells and chance mutations during affinity maturation.…”