Abstract
Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.
Highlights
Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses in swine (IAV-S)
The OV-HA recombinant virus was obtained by inserting the full-length HA gene of IAV-S (H1N1) into ORFV121 locus by homologous recombination between a transfer plasmid pUC57121LR-SIV-HA-loxp-green fluorescent protein (GFP) and the parental orf virus (ORFV) strain IA82 (Figure 1A)
Both HA and NP proteins were detected in non-permeabilized cells; the levels of protein detected were slightly lower than in permeabilized cells (Figure 2B). This decrease was more evident for NP protein than for the HA protein. These findings suggest that while a great proportion of the HA protein expressed by both OV-HA and OV-HA-NP recombinant viruses localizes to the cell surface, and expression of the NP protein is mostly confined to the intracellular compartment
Summary
Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses in swine (IAV-S). IAV-S results in significant economic losses to the swine industry mainly due to weight loss, increased time to market, costs associated with treatment of secondary bacterial infections and mortality. This makes IAV-S one of the top three health challenges to the swine industry affecting pigs in all phases of production [8, 9]. In addition to IAV-S, pigs are susceptible to infection with avian and human IAVs thereby providing a niche for genetic reassortment between avian/human or swine influenza viruses This poses a major threat for emergence of new subtypes as well as increases the risk of zoonotic transmission of IAVs. effective prevention and control measures for IAV infections in swine have direct impacts on both animal and human health
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