Non-responder refers to an individual did not develop their anti HBs, even after administration of a 2 complete series of the HBV vaccine. Due to mutant variants, vaccine failure occurred in numerous reports but the incidence of these mutants were unknown. Primary HBV vaccine series failed for nearly 5% of immunocompetent people. There is no clear vision on nonresponse but certain individuals are at major risk, those with persistent diseases, immunosuppressant medication and genetic predisposition. CD-4 T-helper cells that was obtained from viral peptides played an important role in Human Leukocyte antigen (HLA) along with Major Histocompatibility Complex (MHC) and individuals who failed to respond had defect in T helper cells stimulation or antigen presentation. After administration of a course of vaccine, antibody will be produced against major hydrophilic domain of HBsAg in determinant epitope cluster. As upcoming approaches, antigen dose were increased, alternative vaccination, new adjuvants such as immunostimulatory DNA sequences and accelerating vaccination schedules are followed in practice. Increased dosage vaccines, upgraded immunogenicity, adjuvants, surrogate mechanism, combined vaccines and administration of intradermal vaccines are the relevant approaches for a non-responder. Further studies has to be conducted on HLA alleles that can overcome the obstacles in HBV therapeutics.
