A crucial role of macrophages in the immune responses to oral DNA vaccination against hepatitis B virus in a murine model

in the previous study, we had shown that live oral vaccination with Salmone lla typhimurium delivering plasmid DNA-HBsAg (oral DNA vaccine) evoked a vi gorous T cell response and a weak antibody response with predominant subcla ss IgG2a in mice, suggesting a significant involvement by professional anti gen presenting cells (APC). In the present study, this possibility was furt her studied by infecting peritoneal macrophages (M(phi) with the oral DNA v accine. Although, the infected cells could only express low level of the vi ral antigen, they nevertheless stimulated a vigorous lymphocyte proliferati on of splenocytes from immune mice, induced these cells to elaborate interf eron-gamma and stimulated development of HBV-specific cytotoxicity against target cells expressing the viral antigen. Infusion of the infected M Phi e voked a vigorous Th 1 and cytotoxic T lymphocyte (CTL) response and a weak IgG2a antibody response in mice, which was essentially the same as response to the oral DNA vaccine. In contrast, recombinant protein vaccine evoked a vigorous IgG1 antibody response and a weak T cell response. While, given i ntramuscularly, the same plasmid DNA vaccine as that contained in the oral DNA vaccine evoked a vigorous IgG1 antibody response and a moderate T cell response in these animals. It was concluded that professional APC may orche strate the immune response to live oral DNA vaccine and it was of interest to note that different vaccine formulation and routes of administration evo ke distinct immune response to HBV. (C) 2001 Elsevier Science Ltd. All righ ts reserved.