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Hepatitis B virus core antigen epitopes presented by HLA‐A2 single‐chain trimers induce functional epitope‐specific CD8+ T‐cell responses in HLA‐A2·1/Kb transgenic mice

The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single‐chain trimers (SCT) composed of peptide epitope β2‐microglobulin (β2m) and major histocompatiblity complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)‐A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C18−27 and C107−115. Transfection of NIH‐3T3 cells with pcDNA3.0‐SCT‐C18−27 and SCT‐C107−115 leads to stable presentation of HBcAg epitopes at the cell surface. HLA‐A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg‐specific CTL responses by enzyme‐linked immunospot assay (ELISPOT) and in vitro interferon‐γ release experiments. HBcAg‐specific CTLs from vaccinated HLA‐A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA‐A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA‐A2‐positive HBV carriers.