Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV

Abstract

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been associated with severe disease in humans. Research in mice suggests that FI-RSV may prime for decreased interferon gamma (IFN-γ) production at subsequent infection. Interferon-γ production by peripheral blood mononuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a host naturally susceptible to RSV. Eight-week old male Holstein calves were administered FI-BRSV and mock challenge (V/M, n=6); mock vaccination and BRSV challenge (M/C, n=6) or FI-BRSV and BRSV challenge (V/C, n=7). Vaccine was administered twice at a 2-week interval; challenge followed one month later. On days 0, 5 and 10 postchallenge (PC), PBMC were stimulated in vitro for 24 h with live BRSV, concanavalin A (positive control) or spent media (negative control). Supernatants were assayed for IFN-γ using ELISA. Interferon-γ production by BRSV-stimulated PBMC was increased in M/C and V/C calves as compared to V/M calves on day 5 PC ( p<0.015); and increased in M/C calves compared to V/C and V/M calves on day 10 PC ( p<0.015). Over time postchallenge, a significant increase in IFN-γ production by BRSV-stimulated PBMC was seen in M/C calves ( p<0.025) but not in V/C calves. FI-BRSV vaccination of calves led to diminished IFN-γ production postchallenge. Decreased IFN-γ production may have contributed to impaired viral clearance and enhanced disease in FI-BRSV vaccinated calves.