Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1.
BACKGROUND
Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin gamma and kappa-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against Plasmodium vivax.


METHODS
Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to P. vivax apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses.


RESULTS
IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (P = 0.004, P = 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype.


CONCLUSIONS
Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to P. vivax malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.
Pandey
Janardan P
JP
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA. pandeyj@musc.edu
Morais
Cristiane G
CG
Fontes
Cor Jf
CJ
Braga
Erika M
EM
D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001938:Brazil; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics / Q000276:immunology; D007131:Immunoglobulin Km Allotypes / Q000235:genetics / Q000276:immunology; D016014:Linear Models; D017780:Malaria Vaccines / Q000276:immunology; D016780:Malaria, Vivax / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D008875:Middle Aged; D010641:Phenotype; D010966:Plasmodium vivax / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D018709:Statistics, Nonparametric; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D005819:Genetic Markers; D007074:Immunoglobulin G; D007129:Immunoglobulin Gm Allotypes; D007131:Immunoglobulin Km Allotypes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium