H1N1 INFLUENZA A VIRUS IN SWINE SUPPLEMENTAL RESEARCH PROGRAM
Location: Virus and Prion Research Unit
Title: Heightened adaptive immune responses following vaccination with a temperature-sensitive, live-attenuated influenza virus compared to adjuvanted, whole-inactivated virus in pigs
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 2012
Publication Date: August 31, 2012
Citation: Loving, C.L., Vincent, A.L., Pena, L., Perez, D.R. 2012. Heightened adaptive immune responses following vaccination with a temperature-sensitive, live-attenuated influenza virus compared to adjuvanted, whole-inactivated virus in pigs. Vaccine. 30(40):5830-5838.
Interpretive Summary: The immune system responds differently to different types of vaccines. Influenza virus vaccines for humans include those delivered by a needle into the muscle and one that is misted into the nose. Recently, a new vaccine for influenza was developed for use in pigs that could be given into the nose, similar to that used in humans and horses. The immune response to this new vaccine was compared to the response to the type of vaccine typically used in pigs, which is delivered into the muscle. The immune response can be measured in several ways, including assays performed using serum (liquid part of blood) or using cells from the blood. The immune response to the vaccine could be measured in the serum by day 14 following vaccination if pigs received the vaccine in the nose but these same responses were very low to not detected in serum of pigs given the vaccine in the muscle. Another parameter of the immune response, measured as production of a compound by blood cells, was increased if pigs received the vaccine in the nose but not if they received the other vaccine. These results indicate that this specific vaccine, delivered in the nose of pigs, induces a strong immune response that may be superior to the immune response after vaccination in the muscle.
In the United States there are currently two influenza vaccine platforms approved for use in humans - conventional inactivated virus and live-attenuated influenza virus (LAIV). One of the major challenges for influenza A virus (IAV) vaccination is designing a platform that provides protection across strains. Pandemic H1N1 (pH1N1) IAV swept the globe in 2009 and crossed the species barrier, infecting swine in several countries. Pigs are a natural host for IAV and serve as a model for evaluating immune responses following vaccination and challenge. Recently, a temperature-sensitive (ts) LAIV was developed by introducing modifications in the polymerase genes of a swine-like triple reassortant (tr) virus and when paired with pandemic HA and NA, provided sterilizing immunity upon intratracheal challenge with virulent pH1N1 virus. The utility of ca LAIV is expanded in this report to show vaccination of pigs induced a cell-mediated immune response characterized by an increased number of antigen-specific IFN-gamma secreting cells and expanded T cell populations when compared to pigs vaccinated with a whole inactivated virus (WIV) vaccine. Following challenge, there was a significant increase in the percentage of proliferating lymphocytes in the LAIV group compared to the WIV group following restimulation with pH1N1 in vitro. Also, there was an increase in the percentage of CD4/CD8 double-positive memory T cells in LAIV vaccinated pigs compared to WIV vaccinated pigs. Hemagglutination inhibition titers were significantly higher in the LAIV-vaccinated pigs compared to the WIV vaccinated pigs following a single dose of vaccine. Taken together, these results indicate the ts LAIV vaccine, generated from a triple reassortant IAV, elicits cell-mediated and humoral immune responses in pigs.