This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis B Virus (HBV) remains one of the most common infectious diseases worldwide, ranking behind HIV as the 10th leading cause of death. The serologic pattern, definitions and outcomes of HBV infection are extremely complicated, resulting in widely variable HBV vaccination and treatment recommendations. One marker of prior HBV infection is the antibody to hepatitis B core antigen (anti-HBc). However, certain patients have an "isolated anti-HBc" without any other serologic evidence of HBV, and thus no clear evidence of protective immunity with antibodies to HBV surface antigen (anti-HBs). A high prevalence of isolated anti-HBc has been reported in those with HIV (13-40%), HCV (20 -30%) and HIV/HCV (up to 80%). Studies have shown a proportion of individuals with isolated anti-HBc are carriers of HBV, with detectable viremia or HBV DNA in approximately 10-30%. Our objective is to determine the response to vaccination in those with isolated anti-HBc and without detectable HBV DNA. We will use the antibody titer in response to a single vaccination as indicative of prior infection (high titer, or anamnestic response) or no prior infection (low titer, or primary response). Given the epidemic it is essential that we ascertain the immunologic significance of an isolated anti-HBc, especially in high-risk groups, such as HIV and HCV patients.