Expressed var gene repertoire and variant surface antigen diversity in a shrinking Plasmodium falciparum population.
The var gene-encoded erythrocyte membrane protein-1 of Plasmodium falciparum (PfEMP-1) is the main variant surface antigen (VSA) expressed on infected erythrocytes. The rate at which antibody responses to VSA expressed by circulating parasites are acquired depends on the size of the local VSA repertoire and the frequency of exposure to new VSA. Because parasites from areas with declining malaria endemicity, such as the Amazon, typically express a restricted PfEMP-1 repertoire, we hypothesized that Amazonians would rapidly acquire antibodies to most locally circulating VSA. Consistent with our expectations, the analysis of 5878 sequence tags expressed by 10 local P. falciparum samples revealed little PfEMP-1 DBL1α domain diversity. Among the most commonly expressed DBL1α types, 45% were shared by two or more independent parasite lines. Nevertheless, Amazonians displayed major gaps in their repertoire of anti-VSA antibodies, although the breadth of anti-VSA antibody responses correlated positively with their cumulative exposure to malaria. We found little antibody cross-reactivity even when testing VSA from related parasites expressing the same dominant DBL1α types. We conclude that variant-specific immunity to P. falciparum VSAs develops slowly despite the relatively restricted PfEMP-1 repertoire found in low-endemicity settings.
Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil; Institute of Biotechnology, State University of São Paulo, Al. das Tecomárias s/n, 18607-440 Botucatu, Brazil.
Bianca C
BC
Carlos
Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil.
Wesley L
WL
Fotoran
Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil.
Maria J
MJ
Menezes
Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil; Institute of Biology, University of Campinas, R. Monteiro Lobato 255, Cidade Universitária, 13083-862 Campinas, Brazil.
Fernanda J
FJ
Cabral
Institute of Biology, University of Campinas, R. Monteiro Lobato 255, Cidade Universitária, 13083-862 Campinas, Brazil; Medical Genetic Service, Hospital Professor Edgard Santos, Federal University of Bahia, R. Dr. Augusto Viana, s/n, 40110-060 Salvador, Brazil.
Marcele F
MF
Bastos
Institute of Biology, University of Campinas, R. Monteiro Lobato 255, Cidade Universitária, 13083-862 Campinas, Brazil.
Fabio T M
FTM
Costa
Institute of Biotechnology, State University of São Paulo, Al. das Tecomárias s/n, 18607-440 Botucatu, Brazil.
Jayme A
JA
Sousa-Neto
Institute of Biotechnology, State University of São Paulo, Al. das Tecomárias s/n, 18607-440 Botucatu, Brazil.
Paulo E M
PEM
Ribolla
Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil.
Gerhard
G
Wunderlich
Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil. Electronic address: muferrei@usp.br.
Marcelo U
MU
Ferreira
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood* / Q000378:metabolism; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D016466:CHO Cells; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus; D003430:Cross-Sectional Studies; D019353:Endemic Diseases / Q000706:statistics & numerical data; D014644:Genetic Variation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum
Amazon; Antibodies; PfEMP-1; Plasmodium falciparum; Variant surface antigen