Factors affecting induction of peripheral IFN-gamma recall response to influenza A virus vaccination in pigs

Authors: Bond, Zahra; SANDBULTE, MATTHEW - Iowa State University; KUNZLER SOUZA, CARINE - Orise Fellow; PEREZ, DANIEL - University Of Maryland; Baker, Amy; Loving, Crystal

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/31/2017
Publication Date: 2/2/2017
Citation: Olson, Z.F., Sandbulte, M.R., Kunzler Souza, C., Perez, D.R., Vincent, A.L., Loving, C.L. 2017. Factors affecting induction of peripheral IFN-gamma recall response to influenza A virus vaccination in pigs. Veterinary Immunology and Immunopathology. 185:57-65. doi: 10.1016/j.vetimm.2017.01.009.

Interpretive Summary: In North American swine herd populations 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. In addition, many factors can impact the immune response of pigs to whole-inactivated virus (WIV) vaccines, such as animal age and components of the vaccine. There is no standardized laboratory test to predict protection from different IAV following LAIV vaccination, and variations in pig age and WIV vaccine formulation can affect immune response. We evaluated the production of a protein called IFN-gamma by peripheral blood lymphocytes as a live-animal sample source to evaluate different vaccine formulations. WIV vaccination induced a greater production of IFN-gamma when compared to LAIV vaccination, showing that the assay may not be useful for evaluating LAIV vaccine immune responses. In addition, we showed that WIV vaccine formulation and age at time of vaccination significantly impacted the immune response. We did show that two different methods for evaluating IFN-gamma gave the same results, which is important for other scientists evaluating pig immune responses to vaccination because it gives a more affordable option for evaluating IFN-gamma responses.

Technical Abstract: While T cell contribution to IAV immunity is appreciated, data comparing methods to evaluate IFN-gamma production by IAV-specific T cells elicited following vaccination is limited. To understand the differential immunogenicity between live-attenuated influenza virus (LAIV) and whole-inactivated virus (WIV) vaccines in relation to induction of peripheral T cell responses, ELISpot and ELISA were used to assess IFN-gamma production by peripheral lymphocytes following antigen restimulation. Following restimulation, peripheral blood lymphocytes from WIV-vaccinated pigs had a greater quantity of IFN-gamma secreting cells (SC) and IFN-gamma'secreted compared to LAIV vaccinated and non-vaccinated (NV) pigs. Pig age at time of WIV vaccination significantly impacted peripheral IAV-specific IFN-gamma recall response, as did the inclusion of adjuvant in the WIV vaccine. Collectively, these data indicate that peripheral IAV-specific IFN-gamma recall responses are not predictive of LAIV vaccination status, thus, are unlikely to be a useful surrogate for evaluating LAIV immunogenicity and predicting cross-protection. However, these data suggest that the evaluation of peripheral IFN-gamma recall responses may be useful for investigating factors, such as animal age or vaccine formulation, that affect parenteral vaccine immunogenicity. Overall, results did not differ based upon the assay used to evaluate IFN-gamma recall responses. Therefore, either ELISpot or ELISA could serve as a measure for evaluating IAV-specific IFN-gamma cell-mediated immune responses in swine.