Production of bovine herpesvirus type 1-seronegative latent carriers by administration of a live-attenuated vaccine in passively immunized calves

Abstract

The consequences of the vaccination of neonatal calves with the widely used live-attenuated temperature-sensitive (ts) bovine herpesvirus type 1 (BHV-1) were investigated. The ts strain established acute and latent infections in all vaccinated calves either with or without passive immunity. Four of seven calves vaccinated under passive immunity became clearly BHV-1 seronegative by different serological tests, as did uninfected control calves after the disappearance of maternal antibodies, and they remained so for long periods. A cell-mediated immune response was detected by a BHV-1 gamma interferon assay, but this test failed to detect the seronegative latent carriers (SNLCs). While they are not detected, SNLCs represent a threat for BHV-1-free herds or countries. This study demonstrates that SNLCs can be easily obtained by inoculation with a live-attenuated BHV-1 under passive immunity and that latent carrier animals without any antibody do exist. Consequently, this situation could represent a good model to experimentally produce SNLCs.

FIG. 1

Restriction endonuclease HindIII DNA profiles of nasal viral isolates from the vaccinated calves (group CV and control group V) on the sixth and seventh days after their first dexamethasone injection (PDT) compared with DNA profiles of the BHV-1 ts vaccine strain, the BHV1.1 reference strain Cooper, the virulent strain Iowa, and the field strain Ciney. For calf CV1, the restriction endonuclease analysis was performed on DNA from viruses isolated before the dexamethasone treatment on p.i. day 380 (1*) and on the fourth day PDT (1).

FIG. 2

Evolution of anti-BHV-1 antibody levels obtained by the commercially available indirect ELISA throughout the study, in each experimental group. Group C (top), seven passively immunized control calves; group CV (middle), after vaccination (week 0) with a live-attenuated ts vaccine strain of BHV-1 in seven passively immunized calves (calf CV3 was removed from the study at 14 weeks p.i.); group V (bottom), after vaccination (week 0) with a live-attenuated ts vaccine strain of BHV-1 in five seronegative control calves. The results are expressed as the difference in optical density between positive and control antigens (ΔOD). Horizontal lines indicate the cut-off values: the upper line represents the positive limit, and the lower line represents the negative limit; between the two lines the results are inconclusive. Arrows indicate the times corresponding to the dexamethasone treatment for the different animals.