Plasmodium falciparum VAR2CSA-Specific IgG Subclass Responses Reflect Protection Against Low Birth Weight and Pregnancy-Associated Malaria.

Bernard Tornyigah,Firmine Viwami,Philippe Deloron,Adrian J F Luty,Nadine Fievet,Guillaume Escriou,Nicaise Tuikue Ndam,Achille Massougbodji,Morten A Nielsen,Tania D’Almeida

doi:10.3389/fimmu.2021.610305

Abstract

Sequestration of Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen in the placenta results in poor pregnancy outcomes, including low birth weight and maternal anemia. Antigen-specific antibody-mediated immunity is acquired during successive pregnancies. Thus, evaluating VAR2CSA-specific IgG profiles among pregnant women will increase knowledge on the immunological mechanisms associated with protection, and help in the development of VAR2CSA-based placental malaria vaccines. Using the PAMVAC candidate vaccine antigen, we assessed anti-VAR2CSA IgG subclass responses of a cohort of pregnant Beninese, and analyzed their relationships with pregnancy outcomes. Cytophilic IgG1 and IgG3 responses were the most frequent, with prevalences ranging from 28% (IgG3) up to 50% (IgG1). Elevated levels of VAR2CSA-specific total IgG and cytophilic IgG3 during pregnancy were consistently associated with higher birth weights, whilst high levels of IgG4 were associated with a reduced risk of placental infections. This suggests that protective anti-VAR2CSA IgG responses are coordinated between both cytophilic and non-cytophilic antibodies.

Highlights

Plasmodium falciparum malaria continues to be a significant human disease burden throughout the tropics
The current study made use of samples collected from a subgroup of women drawn from the STOPPAM project initially designed to characterize the pathology of placental malaria, to determine the factors important for optimal use of intermittent preventive treatment of malaria in pregnancy (IPTp) and for vaccine development against pregnancy-associated malaria
The level of antibodies was tested in relation to the following different covariates: maternal age, gravidity, malaria at inclusion, number of peripheral malaria infections identified until the date of plasma collection, parasite density, and at delivery according to pregnancy outcome including anemia and placental infection in mothers; low birth weight, prematurity, intrauterine growth retardation in newborns

Summary

INTRODUCTION

Plasmodium falciparum malaria continues to be a significant human disease burden throughout the tropics. VAR2CSA Specific IgG Subclass Response chondroitin sulfate A (CSA) [3,4,5] This pathophysiological feature, which led to the recognition of placental malaria as a specific syndrome, is frequent in first pregnancies in areas where P. falciparum malaria is highly endemic [6]. Women who have had PM develop anti-VAR2CSA IgG antibodies that protect them from the adverse effects of PM during subsequent pregnancies, making this protein an attractive target for vaccine development [4, 7]. Using measurements of naturally acquired antibody targeting the PAMVAC vaccine Id1-Id2a recombinant antigen on consecutive plasma samples, we analyzed the link between IgG subclasses with different pathological outcomes of pregnancy

METHODS

Ethical Statement

RESULTS

DISCUSSION

ETHICS STATEMENT