Acquisition of natural humoral immunity to P. falciparum in early life in Benin: impact of clinical, environmental and host factors

Abstract

To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas.Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6-to18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6-to18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life.

Effect of nutrient supplementation on the acquisition of humoral immunity to Plasmodium falciparum in young Malawian children

“…In malaria endemic areas, antibodies to malaria antigens increase with age, being higher in adults than in children, but the dynamics of antibody production in infants are less well studied [ 36 ]. The observations that the levels and seroprevalence of antibody to most of the merozoite antigens tested increased between 6 and 18 months of age are in agreement with observations in a case control study conducted in Kenyan children, in which the level of antibodies against MSP1 and PfRh2 increased steadily with increasing age from birth to 2 years [ 37 ], and a cohort study from Benin [ 38 ], in which MSP1 and MSP2 antibody levels showed a constant increase until 18 months of age. In a higher transmission setting, the seroprevalence of antibody to MSP1 reached a peak after 6 months of age, whereas prevalence of antibody to MSP2 peaked at 9 months of age [ 39 ].…”

“…The study found no evidence that nutrient supplementation altered the development of antibody responses to either merozoite antigens or VSA in young children, in accordance with a study conducted on Beninese children of similar age group in whom there was no association between nutritional intake and anti-malarial antibody levels [ 38 ]. Antibody levels or seroprevalence of antibodies to the tested antigens did not differ between the supplementation groups in either unadjusted or adjusted analysis (P > 0.05) except for the seroprevalence in 6 months old children for Rh2A9 (P = 0.044), and that significance was lost in the adjusted analysis.…”

Pattern of antibody responses to Plasmodium falciparum antigens in individuals differentially exposed to Anopheles bites

“…Sarr et al reported that children with higher exposure to Anopheles bites presented a down-regulated IgG1 response to whole Plasmodium extract and to CSP Ag compared to children lower exposed, whereas no effect was observed for the IgG3 isotype response [34]. Dechavanne et al reported that an environmental variable (quantitative index related to the spatiotemporal risk of exposure to Anopheles mosquitoes) was significantly associated with high anti-Plasmodium Ab levels in infants (6-18 month old infants) [13]. A recent study in malaria elimination context also showed a positive association between Anopheles exposure and IgG responses to PfCSP and PfMSP1 Ags [49].…”

“…Immune responses are complex traits and vaccine development requires extensive knowledge of the processes and of the determinants that modulate immune responses in human populations. The effect of age, genetic factors, pathogen co-infection, and nutritional status have been more intensively explored and are recognized to influence anti-Plasmodium Ab responses and to have some association with malaria clinical protection [13][14][15].…”

Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort

“…The study of antibody responses to merozoite candidate vaccine antigens in infant cohorts are of interest as young children are the main victims of P. falciparum and they represent the main target in any malaria vaccination strategy. Previous work conducted in the Tori-Bossito cohort showed that factors such as age, past and current malaria infections, malaria antibody levels at birth, as well as exposure to Anopheles bites were significantly associated with the natural acquisition of anti-malarial IgG1 and IgG3 responses in 6- to 18-month old infants [33]. In the same cohort, the present study aimed to investigate the role of the cytophilic antibody responses acquired against specific P. falciparum candidate vaccine antigens in protection of infants against P. falciparum infection.…”