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

Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has b een associated with severe disease in humans. Research in mice suggests tha t FI-RSV may prime for decreased interferon gamma (IFN-gamma) production at subsequent infection. Interferon-gamma production by peripheral blood mono nuclear cells (PBMC) was measured following challenge of calves vaccinated with FI-BRSV to determine whether a similar mechanism is operative in a hos t naturally susceptible to RSV, Eight-week old male Holstein calves were ad ministered FI-BRSV and mock challenge (V/M, n = 6); mock vaccination and BR SV challenge (M/C, n = 6) or FI-BRSV and BRSV challenge (V/C, n = 7). Vacci ne was administered twice at a 2-week interval; challenge followed one mont h later. On days 0, 5 and 10 postchallenge (PC), PBMC were stimulated in vi tro for 24 h with live BRSV, concanavalin A (positive control) or spent med ia (negative control). Supernatants were assayed for IFN-gamma using ELISA. Interferon-gamma production by BRSV-stimulated PBMC was increased in M/C a nd V/C calves as compared to V/M calves on day 5 PC (p < 0.015); and increa sed 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-gamma production by BRSV-stimulated PBMC was seen in M/C calves (p < 0.025) but not in V/C calv es. FI-BRSV vaccination of calves led to diminished IFN-gamma production po stchallenge. Decreased IFN-gamma production may have contributed to impaire d viral clearance and enhanced disease in FI-BRSV vaccinated calves, (C) 19 99 Elsevier Science Ltd. All rights reserved.