Hepatitis B vaccine responders show higher frequencies of CD8(+) effector memory and central memory T cells compared to non-responders.

Hepatitis B (HB) infection is a major global health problem. There is limited knowledge about HB vaccination-induced immune memory responses. We compared the frequency of CD8+ memory T cell subsets between responders (RSs) and non-responders (NRs) to HB vaccination. Blood samples were collected from RSs and NRs. PBMCs were cultured in the presence of Hepatitis B surface antigens (HBsAg) and PHA for 48 h to restimulate CD8+ memory T cells and T cell memory subsets were detected by flow cytometry using memory cell markers. The frequency of TEM, TCM, and TCM hi was significantly higher in responders compared to non-responders (p = 0.024, 0.022, and 0.047, respectively). Additionally, we report a positive correlation between the frequency of TEM cells in RSs with age and anti-HBsAb level (p = 0.03 and rs = 0.5; p = 0.01 and rs = 0.06). Responders display a higher level of CD8+ T cell-mediated immunity. Therefore, we suggest a possible defect in the formation of immunological CD8+ memory T cells in NRs and it may reduce antibody production compared to the RSs, although more experiments are needed.

Vakili ME ，Mashhadi N ，Ataollahi MR ，Meri S ，Kabelitz D ，Kalantar K ... -  《-》

Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination.

Recombinant hepatitis B surface antigen (HBsAg) was used as a model antigen to evaluate persistence of cellular and humoral immune responses when formulated with three different Adjuvant Systems containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS-21, in an oil-in-water emulsion (AS02B and AS02V), or with liposomes (AS01B). This is an open, 4-year follow-up of a previous randomised, double-blind study. Healthy subjects aged 18-40 years received three vaccine doses on a month 0, 1, 10 schedule and were initially followed for 18 months. A total of 93 subjects (AS02B: n=30; AS02V: n=28; AS01B: n=35) were enrolled in this follow-up and had an additional blood sample taken at Year 4 (NCT02153320). The primary endpoint was the frequency of HBsAg-specific CD4(+) and CD8(+) T-cells expressing cytokines upon short-term in vitro stimulation of peripheral blood mononuclear cells with HBsAg-derived peptides. Secondary endpoints were anti-HBs antibody titres and frequency of HBsAg-specific memory B-cells. A strong and persistent specific CD4(+) T-cell response was observed at Year 4 in all groups. HBsAg-specific CD4(+) T-cells expressed mainly CD40L and IL-2, and to a lesser extent TNF-α and IFN-γ. HBsAg-specific CD8(+) T-cells were not detected in any group. A high, persistent HBsAg-specific humoral immune response was observed in all groups, with all subjects seroprotected (antibody titre ≥10mIU/mL) at Year 4. The geometric mean antibody titre at Year 4 was above 100,000mIU/mL in all groups. A strong memory B-cell response was observed post-dose 2, which tended to increase post-dose 3 and persisted at Year 4 in all groups. The MPL/QS-21/HBsAg vaccine formulations induced persistent immune responses up to 4 years after first vaccination. These Adjuvant Systems offer potential for combination with recombinant, synthetic or highly purified subunit vaccines, particularly for vaccination against challenging diseases, or in specific populations, although additional studies are needed.

Leroux-Roels G ，Van Belle P ，Vandepapeliere P ，Horsmans Y ，Janssens M ，Carletti I ，Garçon N ，Wettendorff M ，Van Mechelen M ... -  《-》

Characterization of hepatitis B virus surface antigen-specific CD4+ T cells in hepatitis B vaccine non-responders.

Suzuki T ，Yamauchi K ，Kuwata T ，Hayashi N ... -  《JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY》

The hepatitis B vaccine protects re-exposed health care workers, but does not provide sterilizing immunity.

Infection with hepatitis B virus (HBV) can be prevented by vaccination with HB surface (HBs) antigen, which induces HBs-specific antibodies and T cells. However, the duration of vaccine-induced protective immunity is poorly defined for health care workers who were vaccinated as adults. We investigated the immune mechanisms (antibody and T-cell responses) of long-term protection by the HBV vaccine in 90 health care workers with or without occupational exposure to HBV, 10-28 years after vaccination. Fifty-nine of 90 health care workers (65%) had levels of antibodies to HBs antigen above the cut-off (>12 mIU/mL) and 30 of 90 (33%) had HBs-specific T cells that produced interferon-gamma. Titers of antibodies to HBs antigen correlated with numbers of HBs-specific interferon-gamma-producing T cells, but not with time after vaccination. Although occupational exposure to HBV after vaccination did not induce antibodies to the HBV core protein (HBcore), the standard biomarker for HBV infection, CD4(+) and CD8(+) T cells against HBcore and polymerase antigens were detected. Similar numbers of HBcore- and polymerase-specific CD4(+) and CD8(+) T cells were detected in health care workers 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 cells in exposed health care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cells were CD45RO(-)CCR7(-)CD127(-) terminally differentiated cells. HBs antigen 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.

Werner JM ，Abdalla A ，Gara N ，Ghany MG ，Rehermann B ... -  《-》

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory.

Elisbão Mdo C ，Baldy JL ，Bonametti AM ，Reiche EM ，Morimoto HK ，Pontello R ，Matsuo T ，Ferelle A ，Neves J ... -  《MEMORIAS DO INSTITUTO OSWALDO CRUZ》