0.017% 0.004% IFN- HBcore-specific CD4 T cells, p 0.01; 0.043% 0.032% vs. with occupational exposure to HBV and in patients who acquired immunity via HBV infection. Most of the HBcore- and polymerase-specific T cells were CD45RO+CCR7?CD127? effector memory Levobupivacaine cells in exposed health-care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cell cells were CD45RO?CCR7?CD127? and terminally differentiated. Conclusions HBsAg vaccine-induced immunity protects against future infection but does not provide sterilizing immunity, as evidenced by HBcore- and polymerase-specific CD8+ T cells in vaccinated health care workers with occupational exposure to HBV. The presence of HBcore- and HBV polymerase-specific T-cell responses is a more sensitive indicator of HBV exposure than detection of HBcore-specific antibodies. strong class=”kwd-title” Keywords: immunization, immune response, T cell, virus Introduction Chronic Hepatitis B virus (HBV) infection is a serious health problem with more than 360 million people infected worldwide and about 1 million deaths per year due to HBV-related liver disease1. Infection with HBV can be prevented by vaccination with HBV surface antigen (HBsAg), which induces HBs-specific antibodies and T cells2C4. A complete 3-dose course of the vaccine induces anti-HBs antibodies in 95% of healthy infants and in 90% of healthy adults, which are considered protective upon HBV exposure5, 6. Anti-HBs titers rapidly decline within the first year after vaccination and more slowly thereafter7. In representative studies conducted 10 to 15 years after Levobupivacaine primary vaccination, 11C63% of vaccinees displayed anti-HBs titers below the cut-off8C10. Breakthrough infections, diagnosed by appearance of antibodies against HBcore antigen (anti-HBc) were infrequent and typically clinically asymptomatic. Furthermore, booster vaccination of those subjects who had lost anti-HBs responses induced recall responses within 2C4 weeks11. Most of these studies focused on vaccinated infants11, 12 in areas where HBV infection is endemic8, 10. In those studies, HBV exposure resulted in natural boosts of the vaccine-induced humoral immune response with 8.2% of the vaccinees experiencing fourfold increases in anti-HBs levels between yearly tests13. Furthermore, children who were born to HBsAg and HBeAg-positive mothers and vaccinated after birth were much more likely to exhibit anti-HBc by their teenage years if they live in endemic areas10. In contrast, much less is known about the longevity of HBsAg-specific immune responses in persons who have been vaccinated as adults and who reside in non-endemic countries. In this population anti-HBs Levobupivacaine titers may wane faster due to absence of natural antigen required to maintain immune memory. Whether and when booster vaccinations are recommended for persons who were vaccinated as adults is Levobupivacaine controversial. Health-care workers are of particular interest in this context because they were among the first to be required to receive the hepatitis B vaccine and thus have the longest follow-up after HBs vaccination. Here, we assessed the immunological mechanisms of long term protection in health-care workers who were vaccinated during adulthood and experienced differential levels of occupational re-exposure to HBV. In addition, we compared their immune responses to those of individuals who acquired natural immunity by recovering from acute HBV infection. Materials and Methods Study cohort Ninety health-care workers were studied for humoral and cellular immune responses 10C28 years after a documented complete course of HBsAg vaccination. Seventy-one health-care workers had received recombinant HBs vaccine (Engerix B or Recombivax), and 14 health-care workers had received a plasma-derived HBs vaccine (Heptavax). For 5 health-care workers the vaccine type was unknown. This immunological analysis was part of a larger recall study of HBsAg vaccinees conducted in the Liver Diseases Branch (ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT01182311″,”term_id”:”NCT01182311″NCT01182311). Twenty-five non-vaccinated patients who had recovered from acute hepatitis B more than 10 years ago, and 10 subjects who had never received the HBsAg vaccine and had never been HBV infected were studied for FGFR3 comparison. All subjects gave written informed consent for research testing under a protocol.