A novel bovine viral vaccine for reproductive safety and performance in cattle

Bovine herpesvirus-1 (BoHV-1), the causative agent of infectious bovine rhinotracheitis (IBR), and bovine viral diarrhea virus (BVDV) vaccines are one of the tools that can be used to improve reproductive efficiency, but ordinary modified-live BoHV-1 components can establish latency, impair fertility or cause abortion. This work evaluated the reproductive safety of a gene-deleted BoHV-1 (gE-/tk-) marker strain used alone or within a multivalent vaccine (BoHV-1 gE-/tk-, recombinant BVDV-1 and BVDV-2 E2 protein, modified live bovine respiratory syncytial virus, inactivated parainfluenza-3). Latency and reactivation were examined in 10 seronegative calves vaccinated twice and later treated with dexamethasone, with non-vaccinated calves and virulent BoHV-1 infection included as negative and positive controls, respectively. Conception effects were assessed in four preclinical heifer trials including vaccinated and non-vaccinated control groups, differing in age and vaccination-to-breeding interval, as well as in two gestational safety studies conducted at different trimesters using either the commercial antigen dose (1X) or a 10-fold increase (10X) of the IBR antigen content. A large field trial on four commercial dairies evaluated conception rate and pregnancy loss in vaccinated animals compared with controls. Vaccine virus was not recovered from nasal swabs, trigeminal ganglia, or tonsils after dexamethasone, whereas challenge calves showed typical reactivation and shedding. Across preclinical trials, vaccination did not reduce conception rate. In both 1X and 10X gestation studies, no abortions occurred, and all viable calves were clinically normal and BoHV-1 seronegative at birth. In the field trial, a farm with extensive records demonstrated a conception rate significantly higher in the vaccinated animals after the second dose compared to controls, while similar rates were observed following the other doses. Pregnancy loss did not differ between vaccinated and control animals. These data demonstrate that the gE-/tk- BoHV-1 marker strain, alone or in a multivalent format, does not establish detectable latency or adversely affect fertility or gestational outcome, supporting its reproductive safety in cattle worldwide.