Early Activation of the Innate Immunity and Specific Cellular Immune Pathways after Vaccination with a Live Intranasal Viral Vaccine and Challenge with Bovine Parainfluenza Type 3 Virus

Abstract

Bovine parainfluenza type 3 (BPIV3) and bovine respiratory syncytial virus (BRSV) may cause bovine respiratory disease (BRD) in very young calves, and therefore vaccination should induce protection at the youngest age and as quickly as possible. This can be achieved by intranasal vaccination with a vaccine containing live attenuated BRSV and BPIV3 virus strains. The objective of this study was to measure gene expression levels by means of RT-qPCR of proteins involved in the innate and adaptive immune response in the nasopharyngeal mucosae after administration of the above-mentioned vaccine and after challenge with BPIV3. Gene expression profiles were different between (i) vaccinated, (ii) nonvaccinated-challenged, and (iii) vaccinated-challenged animals. In nonvaccinated-challenged animals, expression of genes involved in development of disease symptoms and pathology were increased, however, this was not the case after vaccination. Moreover, gene expression patterns of vaccinated animals reflected induction of the antiviral and innate immune pathways as well as an initial Th1 (cytotoxic) cellular response. After challenge with BPIV3, the vaccinated animals were protected against nasal shedding of the challenge virus and clinical symptoms, and in parallel the expression levels of the investigated genes had returned to values that were found before vaccination. In conclusion, in comparison to the virulent wild-type field isolates, the two virus strains in the vaccine have lost their capacity to evade the immune response, resulting in the induction of an antiviral state followed by a very early activation of innate immune and antiviral responses as well as induction of specific cellular immune pathways, resulting in protection. The exact changes in the genomes of these vaccine strains leading to attenuation have not been identified. These data represent the real-life situation and can serve as a basis for further detailed research. This is the first report describing the effects on immune gene expression profiles in the nasal mucosae induced by intranasal vaccination with a bivalent, live BRSV-BPI3V vaccine formulation in comparison to wild-type infection with a virulent BPI3V strain.

Keywords: gene expression; innate immunity; intranasal vaccination; specific immunity.

Figure 1

BPIV3 nasal shedding (mean titer log₁₀ TCID₅₀/mL) post-vaccination and 14 days post-challenge period. Shedding in the vaccinated group before challenge moment is caused by BPIV3 vaccine strain.

Figure 2

Sum of clinical scores per group after challenge.

Figure 3

Comparison of gene expression (fold-change on Y-axis) of vaccinated- versus nonvaccinated-challenged animals. Genes are shown which had significant changes in Ct values five days after vaccination or five days after challenge (see materials and methods). Asterisks indicate non-significant changes according to the arbitrary criteria described in the materials and methods section.

Figure 4

Comparison of gene expression (fold-change on Y-axis) of non-vaccinated control animals versus vaccinated animals after challenge with BPIV3 from day 7 to 12. All genes are shown which had significant changes to Ct values five days after challenge in both groups (see materials and methods). Only IL1R1 was significantly increased in the vaccinated group.