Bordetella bronchiseptica colonization limits efficacy, but not immunogenicity, of live-attenuated influenza virus vaccine and enhances pathogenesis after influenza challenge

Authors: Hughes, Holly; Brockmeier, Susan; Loving, Crystal

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2018
Publication Date: 10/4/2018
Citation: Hughes, H.R., Brockmeier, S., Loving, C.L. 2018. Bordetella bronchiseptica colonization limits efficacy, but not immunogenicity, of live-attenuated influenza virus vaccine and enhances pathogenesis after influenza challenge. Frontiers in Immunology. 9:2255. https://doi.org/10.3389/fimmu.2018.02255.
DOI: https://doi.org/10.3389/fimmu.2018.02255

Interpretive Summary: In North American swine there are numerous different influenza A viruses (IAV) currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides protection against multiple IAV. Live-attenuated influenza virus (LAIV) vaccines provide better protection against multiple IAV than commercially available vaccines making LAIV a candidate for a next-generation swine IAV vaccine. However, bacteria that are present in the respiratory tract of most pigs may interfere with the induction of a protective immune response by LAIV vaccination since it is delivered into the nose. Or, the bacteria may interfere with the ability of the immune system to provide protection that was induced by the vaccine. The bacteria Bordetella bronchiseptica has been shown to alter immune responses in the pig, therefore, we completed a study to determine if B. bronchiseptica interfered with LAIV vaccination or the protection vaccination provides to pigs against IAV challenge. Our results show that B. bronchiseptica does not interfere with the induction of the immune response to the LAIV vaccine, but our results indicate that the Bordetella in the lung may make it difficult for the immune system to provide protection. These results further show the protective benefits of LAIV vaccination against IAV, even in the presence of B. bronchiseptica. Our results also indicate that controlling B. bronchiseptica in swine may be of benefit to limiting the impact of IAV infection.

Technical Abstract: Intranasally administered live-attenuated influenza virus (LAIV) vaccines provide significant protection against heterologous influenza A virus (IAV) challenge. However, LAIV administration can modify the bacterial microbiota in the upper respiratory tract, including alterations in species that cause pneumonia. We sought to evaluate the effect of Bordetella bronchiseptica colonization on LAIV immunogenicity and efficacy in swine, and the impact of LAIV and IAV challenge on B. bronchiseptica colonization and disease. LAIV immunogenicity was not significantly impacted by B. bronchiseptica colonization, but protective efficacy against heterologous IAV challenge in the upper respiratory tract was impaired. Titers of IAV in the nose and trachea of pigs that received LAIV were significantly reduced when compared to non-vaccinated, challenged controls, regardless of B. bronchiseptica infection. Pneumonia scores were higher in pigs colonized with B. bronchiseptica and challenged with IAV, but this was regardless of LAIV vaccination status. While LAIV vaccination provided significant protection against heterologous IAV challenge, the protection was not sterilizing and IAV replicated in the respiratory tract of all LAIV vaccinated pig. The interaction between IAV, B. bronchiseptica, and host led to development of acute-type B. bronchiseptica lesions in the lung. Thus, the data presented do not negate the efficacy of LAIV vaccination, but instead indicate that controlling B. bronchiseptica colonization in swine could limit the negative interaction between IAV and Bordetella on swine health.