Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7 erythrocyte membrane protein 1 family

TY - JOUR

T1 - Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7 erythrocyte membrane protein 1 family

AU - Joergensen, Louise

AU - Turner, Louise

AU - Magistrado, Pamela

AU - Dahlbäck, Madeleine A

AU - Vestergaard, Lasse S

AU - Lusingu, John P

AU - Lemnge, Martha

AU - Salanti, Ali

AU - Theander, Thor G

AU - Jensen, Anja T R

N1 - Keywords: Animals; Antibodies, Protozoan; Binding, Competitive; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Humans; Immunodominant Epitopes; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Protein Structure, Tertiary; Protozoan Proteins; Recombinant Proteins

PY - 2006

Y1 - 2006

N2 - The var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is responsible for antigenic variation and sequestration of infected erythrocytes during malaria. We have previously grouped the 60 PfEMP1 variants of P. falciparum clone 3D7 into groups A and B/A (category A) and groups B, B/C, and C (category non-A). Expression of category A molecules is associated with severe malaria, and that of category non-A molecules is associated with uncomplicated malaria and asymptomatic infection. Here we assessed cross-reactivity among 60 different recombinant PfEMP1 domains derived from clone 3D7 by using a competition enzyme-linked immunosorbent assay and a pool of plasma from 63 malaria-exposed Tanzanian individuals. We conclude that naturally acquired antibodies are largely directed toward epitopes varying between different domains with a few, mainly category A, domains sharing cross-reactive antibody epitopes. Identification of groups of serological cross-reacting molecules is pivotal for the development of vaccines based on PfEMP1.

AB - The var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is responsible for antigenic variation and sequestration of infected erythrocytes during malaria. We have previously grouped the 60 PfEMP1 variants of P. falciparum clone 3D7 into groups A and B/A (category A) and groups B, B/C, and C (category non-A). Expression of category A molecules is associated with severe malaria, and that of category non-A molecules is associated with uncomplicated malaria and asymptomatic infection. Here we assessed cross-reactivity among 60 different recombinant PfEMP1 domains derived from clone 3D7 by using a competition enzyme-linked immunosorbent assay and a pool of plasma from 63 malaria-exposed Tanzanian individuals. We conclude that naturally acquired antibodies are largely directed toward epitopes varying between different domains with a few, mainly category A, domains sharing cross-reactive antibody epitopes. Identification of groups of serological cross-reacting molecules is pivotal for the development of vaccines based on PfEMP1.

U2 - 10.1128/IAI.01187-06

DO - 10.1128/IAI.01187-06

M3 - Journal article

C2 - 17015460

SN - 0019-9567

VL - 74

SP - 6778

EP - 6784

JO - Infection and Immunity

JF - Infection and Immunity

IS - 12

ER -