Antibody responses to α-Gal in African children vary with age and site and are associated with malaria protection

Abstract

Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG1–4 levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk.

Prevalence and Predictors of Malaria in Human Immunodeficiency Virus Infected Patients in Beira, Mozambique

“…This evidence is in line with the current literature [ 20 , 21 ]. In fact, correlation between age and level of malaria transmission is well known also among HIV negative patients: IgG levels, tending to increase with the age [ 22 , 23 , 24 ], influence the severity of malaria and immune response.…”

Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children

“…First, using the same antigen/Ig as the outcome variable at M3. Second, a P. falciparum exposure index was defined as follows [ 27 , 31 ]. Upon examination of antibody responses to the 32 antigen panel [ 26 , 27 ], we selected 28 markers in which IgM responses were M3 > M0 and thus acquired with age (e.g., children > infants) and exposure (e.g., Kintampo > Manhiça).…”

“…Principal component analysis (PCA) of IgM responses to these antigens was performed to construct the corresponding variables, and the first component (PC1) that explained 63% of the variability was selected. Third, a P. falciparum maternal antibody index was defined in subjects < 10 months of age [ 27 , 31 ]. For this, 17 antigens including two VAR2CSA pregnancy-specific antigen constructs were selected which IgG responses were M0 > M3 and thus declined with age (e.g., infants > children) and were higher in infants from the high MTI site (e.g., Kintampo > Manhiça).…”

A Sweet Galactose Transfer: Metabolic Oligosaccharide Engineering as a Tool To Study Glycans in Plasmodium Infection

“…We started by employing these galactose derivatives to study the liver stage of a Plasmodium infection. We considered the importance of the α‐Gal epitope for anti‐malarial immunity and sought to understand whether a change in galactose‐containing glycans was observed on hepatocytes after infection with the Plasmodium parasite . We started by investigating the metabolic incorporation of the synthesized galactose derivatives into human hepatoma cells.…”