Correlations Between The Immune Response To Hepatitis B Vaccine And HLA-DRB1 Genes

Objective:To investigate the correlations between HLA-DRB1 alleles HLA-DRB1~*07,HLA-DRB1~*13,HLA-DRB1~*14,HLA-DRB1~*15 and the feature of immune response to hepatitis B vaccine,thus providing evidence to elucidate the underlying immunogenetic mechanism of hepatitis B vaccine failure.Methods:912 healthy college students of Han nationality from Guangxi province,who had received standard courses of vaccination with recombinant hepatitis B virus vaccine at month 0,1 and 6 soon after they had been admitted into the college,were tested HBV makers(HBsAg,anti-HBs,anti-HBc)and liver function in half a year after their vaccination.The non-or hypor-responders with normal liver function and negative HBV makers,whose S/N of anti-HBs were less than 10,were selected to receive another 20μg doses of recombinant HBsAg vaccine and were examined serum HBV makers again four weeks later. The result showed that the serum HBV makers were still negative.Vaccinees were classified as non-or hypor-responders if their S/N of anti-HBs antibody still remained less than 10,therefore 99 vaccinees were identified.For comparison 136 medium or hyper-responders with normal function and negative HBV makers,whose S/N of anti-HBs was more than 10 at the primary test,were drawn randomly from the same cohort.Serum HBV-DNA of these two group were proven to be negative.Detection of HLA-DRB1~*07,HLA-DRB1~*13, HLA-DRB1~*14,HLA-DRB1~*15 were performed by polymerase chain reaction using sequence specific primer(PCR-SSP)in these individuals who produced sufficient antibodies or fail to mount or only mounted an insufficient antibodies.Results:The allelic frequencies of HLA-DRB1~*07 in nonresponders or hyporresponders group is significantly higher than that in medium or hyperresponders group(16.16%vs 4.41%,P=0.002),while the allelic frequencies of HLA-DRB1~*15 is much lower in the non- and hyporresponders group than that in medium or hyper-responder group(12.12%vs 23.53%, P=0.027);The allelic frequencies of HLA-DRB1~*13 and HLA-DRB1~*14 show no significant differences between the two groups(1.01%vs 3.68%,P=0.389; 8.08%vs 15.44%,P=0.09).Conclusions:1.Non- or hyporresponse to HBV vaccine is related to HLA-DRB1~*07 gene in certain college population of Han nationality from Guangxi province.2.HLA-DRB1~*15 is associated with normal or strong response to HBV vaccine in this cohort.3.No definite relations have been found between HLA-DRB1~*13,HLA-DRB1~*14 and the level of immune response to HBV vaccine in this cohort.