Antibody responses to \u03b1-Gal in African children vary with age and site and are associated with malaria protection

Ruth Aguilar,Gloria P Gómez-Pérez,Núria Balanza,David Dosoo,Ben Gyan,Núria Crespo,Chenjerai Jairoce,Carlota Dobaño,Aintzane Ayestaran,Marta Vidal,Augusto Nhabomba,Itziar Ubillos,Hèctor Sanz,Alfons Jiménez,Luis Izquierdo,Joseph J Campo

doi:10.1038/s41598-018-28325-w

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.

Highlights

Carbohydrates have not classically been considered to be significantly involved in adaptive immune responses, mostly being described as T cell-independent antigens that fail to induce immunological memory and immunoglobulin (Ig) class-switching[1]
In this study we investigated the anti-α-Gal response in children living in malaria-endemic areas of Mozambique (South East Africa) and Ghana (West Africa) who participated in clinical trials of the RTS,S/AS0 vaccine
We examined the effect of age, malaria transmission intensity (MTI) and other variables on anti-α-Gal IgM, IgG, IgG1, IgG2, IgG3 and IgG4 responses, and assessed their association with protection against clinical malaria and the factors affecting it

Summary

Introduction

Carbohydrates have not classically been considered to be significantly involved in adaptive immune responses, mostly being described as T cell-independent antigens that fail to induce immunological memory and immunoglobulin (Ig) class-switching[1]. Recent works showed the presence of precursors involved in glycoconjugate biosynthesis[11,12] and identified new glycosylations in the parasite surface[13,14,15] Some of these sugars modify important antigens in the fight against malaria, such as the circumsporozoite surface protein (CSP), which is the main component of the RTS,S vaccine[16] and is O-fucosylated in malaria sporozoites. Anti-α-Gal antibodies are largely produced in response to cross-reactive epitopes present in commensal bacteria or food[21,22], being the most abundant natural antibody in humans, constituting 1–5% of circulating IgM and IgG in healthy adults[21]. We examined the effect of age, malaria transmission intensity (MTI) and other variables on anti-α-Gal IgM, IgG, IgG1, IgG2, IgG3 and IgG4 responses, and assessed their association with protection against clinical malaria and the factors affecting it

Methods

Results

Conclusion