Humoral Response to Recombinant Hepatitis B Virus Vaccine at Birth: Role of HLA and Beyond

From 1991 to 1998 we vaccinated 4835 neonates against hepatitis B virus (HBV) and monitored their humoral response to the recombinant vaccine. In a sample of 184 of these babies we studied the association between HLA class I and II genomic polymorphisms and humoral response to the vaccine and the association between the response and immune-mediated diseases. A subgroup of 96 babies also underwent HLA class III (C4A and C4B) typing. Four levels of humoral response were identified, each with a peculiar MHC restriction. Different HLA products seem to act as agonists (C4AQ0 and HLA-DQB1*02) or antagonists (C4AQ0, HLA-DQB1*02, and HLA-DRB1*11, DQB1*0301) in lowering humoral response to HBV vaccine. The group of responders was characterized more for lacking “nonresponder” alleles than for having specific “responder” ones. Tolerance to HBV peptides may have clinical implications, possibly being a marker for babies with a genetic risk of immunopathologies. In fact, many of the poor responders carried from two to four HLA-DQαβ heterodimers predisposing to insulin-dependent diabetes mellitus and celiac disease. Two true nonresponders suffered from allergies and two slow responders had transient episodes of hyperglycemia.