Acquisition of antibody isotypes againstPlasmodium falciparumblood stage antigens in a birth cohort

Abstract

Information on the period during which infants lose their maternally derived antibodies to malaria and begin to acquire naturally their own immune responses against parasite antigens is crucial for understanding when malaria vaccines may be best administered. This study investigated the rates of decline and acquisition of serum antibody isotypes IgG1, IgG2, IgG3, IgG4, IgM and IgA to Plasmodium falciparum antigens apical membrane antigen (AMA1), merozoite surface proteins (MSP1-19, MSP2 and MSP3) in a birth cohort of 53 children living in an urban area in the Gambia, followed over the first 3 years of life (sampled at birth, 4, 9, 18 and 36 months). Antigen-specific maternally transferred antibody isotypes of all IgG subclasses were detected at birth and were almost totally depleted by 4 months of age. Acquisition of specific antibody isotypes to the antigens began with IgM, followed by IgG1 and IgA. Against the MSP2 antigen, IgG1 but not IgG3 responses were observed in the children, in contrast with the maternally derived antibodies to this antigen that were mostly IgG3. This confirms that IgG subclass responses to MSP2 are strongly dependent on age or previous malaria experience, polarized towards IgG1 early in life and to IgG3 in older exposed individuals.

A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine

“…Efficacy against clinical malaria has also been shown to correlate with peripheral blood monocyte-to-lymphocyte ratios before vaccination [37]. Total anti-CSP immunoglobulin G (IgG) responses were measured which poses another limitation as the duration and effectiveness of the RTS,S-induced antibody responses may depend on IgG subclass [38,39]. By combining our model for the decay of anti-CSP antibody titres, the estimated relationship between antibodies and efficacy, and a model for the acquisition of immunity to clinical malaria [5], we were able to demonstrate associations between the magnitude and duration of efficacy on a number of covariates.…”

Evaluation of Immunoglobulin G Responses to Plasmodium falciparum and Plasmodium vivax in Malian School Children Using Multiplex Bead Assay

“…At birth, children in malaria-endemic regions tend to have significant titers of maternal antimalarial antibodies, but these generally are lost by approximately the 6th month of life. 22,23 In high-transmission settings, children are almost inevitably exposed to malaria at a young age, and begin developing IgG antibodies based on their own adaptive immune responses. As shown in Figure 4 for this sample of Malian children aged 5-16 years, we found a substantial increase in the mean P. falciparum antibody levels as age increased.…”

Age-Dependent IgG Subclass Responses to Plasmodium falciparum EBA-175 Are Differentially Associated with Incidence of Malaria in Mozambican Children

“…Future studies need to investigate in more depth how different antibody isotypes induced by P. falciparum are transferred from the mother to the infant and the kinetics of production in early life (14). Different IgG isotypes appear to inherently vary in their capacity to transfer to the fetus (18), with IgG1 being the most efficiently transported subclass and IgG2 the least (51), and these differences may partly explain the susceptibility of newborns to various pathogens.…”