IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria.
In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.
Taylor
R R
RR
Institute of Cell, Animal and Population Biology, Division of Biological Sciences, University of Edinburgh, United Kingdom.
Allen
S J
SJ
Greenwood
B M
BM
Riley
E M
EM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood*; D000953:Antigens, Protozoan; D000954:Antigens, Surface / Q000276:immunology; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood*; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015995:Prevalence; D015800:Protozoan Proteins / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium