T-cell Responses in Seronegative Partners of HBV Patients
T-cell Responses in Seronegative Partners of HBV Patients
The hepatitis B virus (HBV) is frequently transmitted by sexual intercourse. Thus, HBV-guidelines recommend vaccination. However, we have identified healthy hepatitis B surface antigen and anti-HBc-negative unvaccinated sexual partners of patients with chronic hepatitis B. We investigated whether HBV-specific cellular immune responses were present that could explain the apparent protection against HBV infection. In six anti-HBc-negative HBV-exposed sexual partners, HBV-specific T-cell responses were studied by proliferation assay and cytometric bead array after stimulation with 74 overlapping peptides spanning the HBV core, pre-S and S-encoding regions. Eleven HBV-unexposed individuals served as negative controls. HBV-DNA was undetectable in serum and peripheral blood mononuclear cells in all cases. HBV-specific cytokine secretion was observed in 4/6 seronegative partners, but only in 1/11 controls. Proliferative responses were detectable in 5/6 partners and 0/11 controls. HBV-specific cytokine secretion exists in healthy seronegative virus-exposed individuals. HBV core-directed immune responses indicate past, but controlled viral replication. T-cell immunity may prevent clinical manifestation of HBV infection in the absence of humoral immunity.
The hepatitis B virus (HBV) is one of the most infectious viruses with frequent sexual transmission. Unprotected sexual intercourse is associated with an estimated risk of infection of at least 20%. The incidence of HBV infection rises after the onset of sexual activity in puberty and peaks in the age group of 25–29 years. Overall, sexual transmission is the most frequent mode of infection in Germany and accounts for 34% of cases. Importantly, it is associated with the lack of pre-emptive vaccination. Thus, recent HBV-guidelines strongly recommend vaccination of sexual partners to prevent infection. Vaccination with recombinant hepatitis B surface antigen (HBsAg) induces a humoral immune response with generation of antibodies against HBsAg (anti-HBs). An anti-HBs >10 IU/mL is believed to protect from HBV infection. However, there are healthy seronegative sexual partners of patients with chronic hepatitis B who have never been vaccinated, but are negative for HBsAg, anti-HBs, anti-HBc (antibodies against hepatitis B core protein) and HBV-DNA. Thus, the present study investigated whether such healthy, but HBV-exposed subjects without any virus-specific humoral immune response show HBV-specific cellular immune responses possibly explaining the absence of signs of HBV infection.
In hepatitis C, virus-specific T-cell responses could be detected in exposed seronegative family members, in healthy individuals after occupational exposure. or in seronegative drug users. Hepatitis C virus (HCV)-specific CD4 and CD8 lymphocytes were detected at low and sometimes at transient levels, but indicated an immunological memory after subclinical infection presumably providing antiviral protection by prompt HCV-specific effector function in vivo. Similar T-cell responses were observed in homosexual and heterosexual seronegative partners of HIV-infected individuals or seronegative HIV-exposed health care workers.
The present study aimed to investigate HBV-specific T-cell responses by usage of overlapping HBV-related peptides spanning the HBV core, pre-S, and S encoding regions to study a large number of potential epitopes and facilitate a comprehensive screening of TH1 and TH2 cytokine secretion. The results showed HBV-specific TH1 cytokine secretion and hepatitis B core-directed immune responses indicating past, but controlled viral replication in healthy seronegative HBV-exposed individuals.
Abstract and Introduction
Abstract
The hepatitis B virus (HBV) is frequently transmitted by sexual intercourse. Thus, HBV-guidelines recommend vaccination. However, we have identified healthy hepatitis B surface antigen and anti-HBc-negative unvaccinated sexual partners of patients with chronic hepatitis B. We investigated whether HBV-specific cellular immune responses were present that could explain the apparent protection against HBV infection. In six anti-HBc-negative HBV-exposed sexual partners, HBV-specific T-cell responses were studied by proliferation assay and cytometric bead array after stimulation with 74 overlapping peptides spanning the HBV core, pre-S and S-encoding regions. Eleven HBV-unexposed individuals served as negative controls. HBV-DNA was undetectable in serum and peripheral blood mononuclear cells in all cases. HBV-specific cytokine secretion was observed in 4/6 seronegative partners, but only in 1/11 controls. Proliferative responses were detectable in 5/6 partners and 0/11 controls. HBV-specific cytokine secretion exists in healthy seronegative virus-exposed individuals. HBV core-directed immune responses indicate past, but controlled viral replication. T-cell immunity may prevent clinical manifestation of HBV infection in the absence of humoral immunity.
Introduction
The hepatitis B virus (HBV) is one of the most infectious viruses with frequent sexual transmission. Unprotected sexual intercourse is associated with an estimated risk of infection of at least 20%. The incidence of HBV infection rises after the onset of sexual activity in puberty and peaks in the age group of 25–29 years. Overall, sexual transmission is the most frequent mode of infection in Germany and accounts for 34% of cases. Importantly, it is associated with the lack of pre-emptive vaccination. Thus, recent HBV-guidelines strongly recommend vaccination of sexual partners to prevent infection. Vaccination with recombinant hepatitis B surface antigen (HBsAg) induces a humoral immune response with generation of antibodies against HBsAg (anti-HBs). An anti-HBs >10 IU/mL is believed to protect from HBV infection. However, there are healthy seronegative sexual partners of patients with chronic hepatitis B who have never been vaccinated, but are negative for HBsAg, anti-HBs, anti-HBc (antibodies against hepatitis B core protein) and HBV-DNA. Thus, the present study investigated whether such healthy, but HBV-exposed subjects without any virus-specific humoral immune response show HBV-specific cellular immune responses possibly explaining the absence of signs of HBV infection.
In hepatitis C, virus-specific T-cell responses could be detected in exposed seronegative family members, in healthy individuals after occupational exposure. or in seronegative drug users. Hepatitis C virus (HCV)-specific CD4 and CD8 lymphocytes were detected at low and sometimes at transient levels, but indicated an immunological memory after subclinical infection presumably providing antiviral protection by prompt HCV-specific effector function in vivo. Similar T-cell responses were observed in homosexual and heterosexual seronegative partners of HIV-infected individuals or seronegative HIV-exposed health care workers.
The present study aimed to investigate HBV-specific T-cell responses by usage of overlapping HBV-related peptides spanning the HBV core, pre-S, and S encoding regions to study a large number of potential epitopes and facilitate a comprehensive screening of TH1 and TH2 cytokine secretion. The results showed HBV-specific TH1 cytokine secretion and hepatitis B core-directed immune responses indicating past, but controlled viral replication in healthy seronegative HBV-exposed individuals.