Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production

Vaccine. 2003 Mar 7;21(11-12):1158-64. doi: 10.1016/s0264-410x(02)00560-1.


The objective of this study was to determine the effect of vaccination with commercially-available multivalent vaccines containing either modified-live (MLV) bovine herpesvirus-1 (BHV-1) (Bovishield) or MLV plus killed (MLV + K) BHV-1 (Reliant Plus) on protection against challenge at 5 days after a single vaccination. An additional objective was to determine whether cell-mediated immunity as measured by virus-specific interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) was associated with any early protection induced by vaccination. Clinical signs, serum neutralizing (SN) titers, and nasal virus isolation (VI) titers were also measured. The 12-16-week-old dairy cross-calves seronegative for antibodies to BHV-1 were vaccinated with a multivalent vaccine containing MLV BHV-1 (n = 19), a multivalent vaccine containing MLV + K BHV-1 (n = 19), or a control multivalent vaccine not containing BHV-1 (n = 10) on day 0 and challenged intranasally on day 5. PBMC were isolated on days 0, 3, 5, 8, 10, 14 and 19. PBMC were incubated in vitro with spent media, live BHV-1, or heat-inactivated BHV-1 for 72 h. Supernatants were assayed for bovine IFN-gamma by ELISA. Bovine herpesvirus-1-specific IFN-gamma production was expressed as percent of the kit positive control, with value for spent media subtracted. Clinical signs were monitored daily. Serum VN titers were measured on days 0-5 and 19. Nasal VI titer was measured every other day from days 5 to 19. Interferon gamma production was higher on day 5, and was significantly increased post-challenge, in both vaccine groups compared to controls. There was no difference between vaccine groups on any day. There was no significant difference in SN titer among groups on any day. Virus isolation titer was significantly higher in controls on days 6 and 8 compared to both vaccine groups. Temperatures were significantly higher and nasal discharge was present more often post-challenge in controls compared to vaccine groups. Vaccination 5 days prior to challenge with commercially-available vaccine containing MLV or MLV + K BHV-1 was associated with increased BHV-1-specific IFN-gamma production, decreased viral shedding, lower temperatures and less nasal discharge post-challenge. Cell mediated immune responses as measured by IFN-gamma production are stimulated rapidly following BHV-1 vaccination of calves.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis*
  • Antibodies, Viral / immunology
  • Cattle
  • Cattle Diseases / prevention & control*
  • Fever / etiology
  • Herpesviridae Infections / prevention & control
  • Herpesviridae Infections / veterinary*
  • Herpesvirus 1, Bovine / immunology*
  • Herpesvirus 1, Bovine / isolation & purification
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Nasal Cavity / virology
  • Nasal Mucosa / metabolism
  • Vaccination / veterinary*
  • Vaccines, Attenuated / immunology
  • Vaccines, Combined / immunology
  • Vaccines, Inactivated / immunology
  • Viral Vaccines / immunology*


  • Antibodies, Viral
  • Vaccines, Attenuated
  • Vaccines, Combined
  • Vaccines, Inactivated
  • Viral Vaccines
  • Interferon-gamma