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Non-Responsiveness To Hepatitis B Vaccination In Adolescents: Role Of HLA-DRB1 Alleles

Hartono Gunardi, Turyadi Turyadi, Susan Irawati Ie, David Handojo Muljono.

Abstract
Background. Some healthy individuals do not respond to hepatitis B vaccination. The precise mechanism for non-responsiveness is unknown yet, although it has been associated with human leukocyte antigen (HLA), a host factor. This study investigated the association between HLA-DRB1 alleles and hepatitis B vaccine response in adolescents.
Methods. Senior high-school and college students aged 15-20 years old who had received primary hepatitis B vaccination during 0-5 year old with non-protective anti-HBs were recruited via stratified random sampling for Hepatitis B marker screening and booster administration. Anti-HBs was tested one month afterwards. All non-responders and randomly selected high responders were typed for HLA-DRB1. Non-responders were given additional booster doses and anti-HBs was evaluated one month afterwards.
Results. There were 213 students who had completed primary hepatitis B vaccination at 0-5 year age screened for Hepatitis B markers. Among these, 89 were negative for HBsAg, anti-HBc and anti-HBs, thus eligible for enrollment. However, only 84 gave their consent and participated in this study. Among 84 subjects, three did not respond to one dose of hepatitis B booster vaccine and were categorized as non-responders. The HLA-DRB1 alleles identified in non-responders were HLA-DRB1*0403, DRB1*1219, and DRB1*1301. Non-responsiveness to hepatitis B vaccine was not permanent, all non-responders seroconverted after administration of two or three doses of a booster vaccine.
Discussion. This study confirmed the association between certain HLA-DR alleles and lack of antibody response to hepatitis B vaccine.
Conclusions. The presence of certain HLA-DRB1 alleles in non-responders demonstrated that the HLA pattern influenced the immune response to hepatitis B vaccination. Administration of additional booster doses to non-responders could elicit protective immunity.

Key words: hepatitis B, vaccination, booster, adolescent, HLA, non-responsiveness



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