Cell-mediated and humoral immune responses to bovine herpesvirus type 1 and bovine viral diarrhea virus in calves following administration of a killed-virus vaccine and bovine herpesvirus type 1 challenge

Abstract

OBJECTIVE To evaluate cell-mediated and humoral immune responses of calves receiving 2 doses of a dual-adjuvanted vaccine containing inactivated bovine herpesvirus type 1 (BHV1) and bovine viral diarrhea virus types 1 (BVDV1) and 2 (BVDV2) before and after exposure to BHV1. ANIMALS 24 Holstein steers negative for anti-BHV1 antibodies and proliferative cell-mediated immune responses against BHV1 and BVDV. PROCEDURES Calves were randomly assigned to 3 groups. The vaccinated group (n = 10) received 2 doses of vaccine on days 0 and 21. Control (n = 10) and seeder (4) groups remained unvaccinated. Calves were commingled during the study except for the 3-day period (days 53 to 55) when seeders were inoculated with BHV1 (1.04 × 107 TCID50, IV) to serve as a source of virus for challenge (days 56 through 84). Rectal temperature and clinical illness scores were monitored, and blood and nasal specimens were obtained for determination of clinicopathologic and immunologic variables. RESULTS After BHV1 challenge, mean rectal temperature and clinical illness scores were lower for vaccinates than controls. In vaccinates, antibody titers against BHV1 and BVDV2, but not BVDV1, increased after challenge as did extracellular and intracellular interferon-γ expression, indicating a T helper 1 memory response. Additional results of cell marker expression were variable, with no significant increase or decrease associated with treatment. CONCLUSIONS AND CLINICAL RELEVANCE Calves administered 2 doses of a killed-virus vaccine developed cell-mediated and humoral immune responses to BHV1 and BVDV, which were protective against disease when those calves were subsequently exposed to BHV1.

Evaluation of Antigenic Comparisons Among BVDV Isolates as it Relates to Humoral and Cell Mediated Responses

“…As previously discussed, antigenic similarity is typically determined using serological assays such as VNT, whereas CMI is generally determined by the induction of IL-2, IFN-γ, and CD25 labeling ( 25 – 27 , 29 , 30 ). To date, no studies have measured differences in CMI responses against multiple BVDV strains to better understand if there is a strain specific component to CMI or if it is a generalized cellular response to BVDV antigens and contributes to a more broadly protective response.…”

“…Since the current assay evaluated mRNA expression and not protein accumulation, the timing post stimulation is targeted at IFN-γ which is typically involved in CMI responses and has previously been optimized for the current assay ( 27 ). Although, this is a limiting factor of the current assay as multiple cytokines cannot be measured, but in general, IFN-γ is a characteristic cytokine produced by memory T cells during an antigen recall response ( 25 – 27 , 29 , 30 , 39 , 40 ). To this end, IFN-γ mRNA expression may vary in the different PBMCs evaluated in the current study, the timing may also vary in each respective PBMC population, and each BVDV strain may vary in timing of induction of IFN-γ mRNA expression.…”

“…The two groups of cattle were utilized to evaluate if similar trends in CMI responses were observed in cattle that differed in the frequency they were vaccinated. CMI responses have been previously reported and generally are characterized by the induction of IL-2, IFN-γ, and CD25 labeling in vaccinated calves as compared to non-vaccinates ( 25 – 27 , 29 , 30 ). Therefore, these measures were used in the current study to evaluate differences among different BVDV strains as measures of antigenic differences in different PBMC populations.…”

Response to Bovine Viral Diarrhea Virus in Heifers Vaccinated with a Combination of Multivalent Modified Live and Inactivated Viral Vaccines

“…The increased protection provided by BVDV MLV vaccines is thought to be associated with a more robust CMI response as determined by cell-mediated recall responses measured by the production of IFN-γ and expression of CD25+ as markers for activated T-lymphocytes. Previous literature has suggested that both MLV and KV containing BVDV exhibit a recall memory response as observed by inducing increased expression of IFN-γ in T-cell subsets after re-stimulation with BVDV in vitro [ 25 , 26 , 27 ]. It should be noted that while it has been suggested that inactivated BVDV vaccines induce a CMI response, these results are discordant with the in vivo data that support that MLV vaccines induce a more effective response.…”