Public Release Type:
Journal
Publication Year: 2014
Authors:
Lee WM,
Lok ASF,
Terrault N,
Khalili M,
Sterling RK,
Carithers R,
Chang KM,
Feld JJ,
Keith J,
Kim WR,
Kowdley KV,
Lau DT,
Levine DL,
Park JJ,
Smith C,
Valiga ME,
Wahed AS,
Wong DK
Studies:
Hepatitis B Research Network
Background and Aims: Hepatitis B virus (HBV) is cleared with long-lasting antiviral T cell memory whereas HBV persists with dysfunctional antiviral T cells. Recently, memory T cell responses to HBV core and reverse transcriptase (RT) in vaccinated anti-HBcnegative healthcare workers (Werner, Gastro 2013) suggested that HBV vaccination is protective but not sterilizing. Here, we looked for immune correlates of vaccine-mediated immunity relative to immune dysregulation in chronic hepatitis B (cHBV). Methods: Peripheral lymphocytes from 17 HBV vaccinees and 168 cHBV participants of the NIDDK-sponsored Hepatitis B Research Network (HBRN) were analyzed for lymphoproliferation and IFNg/IL10 production following stimulation with HBV peptide pools (S, preS, preC, Core, RT) and immune phenotype by multi-color FACS. Statistical analyses included Mann Whitney U and Fisher’s Exact or Chi-square. Results: HBV-vaccinees displayed greater proliferative, IFNg+ and IL10+ T cell responses to S (included in HBV vaccine) and non-S antigens (not included in HBV vaccine) as shown below. HBV-vaccinees displayed both CD4 and CD8 T cell responses to HBV-RT suggestive of immune induction during HBV infection in-vivo. Compared to vaccinees, cHBV participants displayed increased %Foxp3+/CD4+ Tregs (p = 0.017), reduced %CD56+CD16− NK-cells (p = 0.0001) and reduced %mDC (p = 0.004) with differential expression in activating, inhibitory and/or costimulatory molecules. Conclusions: HBV-specific T cells in HBV-vaccinees show greater virus-specific proliferation and IFNg as well as IL-10 production compared to cHBV participants who display differential immune regulatory phenotype. T cell response to HBV non-S antigens in HBV vaccinees also suggest protective but non-sterilizing vaccinemediated immunity.