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

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 alpha-galactose (alpha-Gal) (Gal alpha 1-3Gal beta 1-4GlcNAc-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 alpha-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-alpha-Gal IgM, IgG and IgG(1-4) 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 alpha-Gal responses. There was evidence for a possible protective role of anti-alpha-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to alpha-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.