TY - JOUR

T1 - A conformational epitope in placental malaria vaccine antigen VAR2CSA

T2 - What does it teach us?

AU - Doritchamou, Justin Y A

AU - Renn, Jonathan P

AU - Hviid, Lars

AU - Duffy, Patrick E

N1 - Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

PY - 2023

Y1 - 2023

N2 - VAR2CSA is the Plasmodium falciparum variant surface antigen that mediates binding of infected erythrocytes to chondroitin sulfate A (CSA) and their sequestration in intervillous spaces of the placenta, leading to placental malaria (PM). Relatively high polymorphism in VAR2CSA sequences has hindered development of a vaccine that induces broadly neutralizing immunity. Recent research has highlighted that a broadly reactive human monoclonal antibody, called PAM1.4, binds to multiple conserved residues of different subfragments of VAR2CSA, forming a conformational epitope. In this short perspective, we describe evidence that residues located in the interdomain-1 fragment of VAR2CSA within the PAM1.4 binding epitope might be critical to broad reactivity of the antibody. Future investigation into broadly reactive anti-VAR2CSA antibodies may be important for the following: (1) identification of similar conformation epitopes targeted by broadly neutralizing antibodies; and (2) understanding different immune evasion mechanisms used by placenta-binding parasites through VAR2CSA polymorphism in critical epitopes.

AB - VAR2CSA is the Plasmodium falciparum variant surface antigen that mediates binding of infected erythrocytes to chondroitin sulfate A (CSA) and their sequestration in intervillous spaces of the placenta, leading to placental malaria (PM). Relatively high polymorphism in VAR2CSA sequences has hindered development of a vaccine that induces broadly neutralizing immunity. Recent research has highlighted that a broadly reactive human monoclonal antibody, called PAM1.4, binds to multiple conserved residues of different subfragments of VAR2CSA, forming a conformational epitope. In this short perspective, we describe evidence that residues located in the interdomain-1 fragment of VAR2CSA within the PAM1.4 binding epitope might be critical to broad reactivity of the antibody. Future investigation into broadly reactive anti-VAR2CSA antibodies may be important for the following: (1) identification of similar conformation epitopes targeted by broadly neutralizing antibodies; and (2) understanding different immune evasion mechanisms used by placenta-binding parasites through VAR2CSA polymorphism in critical epitopes.

KW - Female

KW - Pregnancy

KW - Humans

KW - Placenta/metabolism

KW - Epitopes/genetics

KW - Malaria Vaccines

KW - Malaria, Falciparum/prevention & control

KW - Plasmodium falciparum/metabolism

KW - Antigens, Protozoan

KW - Malaria

KW - Antibodies, Protozoan

KW - Chondroitin Sulfates/metabolism

KW - Erythrocytes/parasitology

U2 - 10.1371/journal.ppat.1011370

DO - 10.1371/journal.ppat.1011370

M3 - Journal article

C2 - 37228009

VL - 19

JO - P L o S Pathogens (Online)

JF - P L o S Pathogens (Online)

SN - 1553-7374

IS - 5

M1 - e1011370

ER -