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Title:   Author  item
                                            Braucher, Douglasitem
                                            Henningson, Jamieitem
                                            Loving, Crystalitem
                                            Baker, Amyitem
                                            KIM, E - University Of Pittsburghitem
                                            STEITZ, J - University Of Pittsburghitem
                                            GAMBOTTO, A - University Of Pittsburghitem
                                            Kehrli Jr, Marcus
  Submitted to: Research Workers in Animal Diseases Conference Proceedings
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 9/26/2011
                                    Publication  Date: 12/4/2011
                                    Citation: Braucher, D.R., Henningson, J.N., Loving, C.L., Vincent, A.L., Kim, E., Steitz, J., Gambotto, A.A., Kehrli, Jr., M.E. 2011. Intranasal vaccination with Ad5-encoding influenza HA elicits sterilizing immunity to homologous challenge and partial protection to heterologous challenge in pigs [abstract]. Conference of Research Workers in Animal Diseases. Paper No. 131.Interpretive Summary:
                                Technical Abstract: Vaccine availability during the 2009 H1N1 pandemic highlighted the lengthy production time of traditional vaccine. Replication defective adenovirus (Ad5) constructs with influenza genes have been investigated as candidate vaccines with rapid production potential. However, the primary model used for investigation of Ad5-influenza vaccines has focused on subcutaneous immunization in mice. We compared the efficacy of a single intranasal dose of an Ad5 vaccine to traditional intramuscular (IM) administration of an adjuvanted whole inactivated virus (WIV) vaccine following homologous and heterologous challenge in swine. Pigs were immunized with an Ad5 construct containing a codon optimized hemagglutinin gene (Ad5-HA) of A/CA/04/2009 (H1N1). Adjuvanted, WIV (A/CA/04/09) vaccine was given IM with a boost at day 21 post vaccination. Animals were challenged intranasally at 42 days post vaccination with A/CA/04/09 or A/swine/MN/02011/08 (MN, H1N2). The Ad5-HA vaccine provided sterilizing immunity to homologous challenge. Following heterologous challenge (MN) in Ad5-HA vaccinated pigs, macroscopic lung lesions were not different than non-vaccinated/challenged controls (NV/MN), but nasal virus shedding was reduced by 3 days post infection (dpi) and undetectable in lung lavage fluid at 5 dpi. The Ad5-HA vaccine induced a mucosal IgA response towards homologous CA09 virus and primed an antigen-specific T-cell response against both challenge viruses. Hemagglutination inhibiting titers were measurable in sera of WIV but not Ad5-HA vaccinated pigs. The WIV vaccinated pigs displayed vaccine associated enhanced respiratory disease (VAERD) following heterologous challenge (MN) characterized by enhanced macroscopic lung lesions and elevated non-neutralizing antibody titers to heterologous virus (MN) in nasal wash, BALF and sera. This study shows for the first time that a single intranasal vaccination with an Ad5 construct encoding the HA of influenza can provide complete protection to homologous challenge and partial protection to heterologous challenge, as opposed to VAERD, which can occur with adjuvanted WIV vaccine.


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