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Title:   Author  item
                                            Braucher, Douglasitem
                                            Henningson, Jamieitem
                                            Loving, Crystalitem
                                            Baker, Amyitem
                                            KIM, EUM - University Of Pittsburgh Medical Centeritem
                                            STEITZ, JULIA - Aachen Universityitem
                                            GAMBOTTO, ANDREA - University Of Pittsburgh Medical Centeritem
                                            Kehrli Jr, Marcus
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/20/2012
                                    Publication  Date: 11/1/2012
                                    Citation: Braucher, D.R., Henningson, J.N., Loving, C.L., Vincent, A.L., Kim, E., Steitz, J., Gambotto, A.A., Kehrli, Jr., M.E. 2012. Intranasal vaccination with replication-defective adenovirus type 5 encoding influenza virus hemagglutinin elicits protective immunity to homologous challenge and partial protection to heterologous challenge in pigs. Clinical and Vaccine Immunology. 19(11):1722-1729.Interpretive Summary: There are a large number of different strains of influenza (Flu) virus that cause disease in North American swine. Each of these strains "looks" a little different to the pig's immune system, and is different enough that it can often avoid the immune response. A vaccine for Flu can be used by swine producers to help protect their pigs, but the current type of vaccine that can be used does not provide very good protection to these different strains. New types of vaccines that could protect from infection to a variety of Flu strains is highly desired by producers. We investigated one such new vaccine and compared it to the current type of vaccine that can be used in pigs. Our results show that the new vaccine type provided some protection to a different strain of Flu and this protection could decrease the transmission of the virus between pigs. However, the old vaccine type did not provide protection and disease was actually more severe in that group. Thus, our data show that this new vaccine type may be useful for swine producers to protect against different flu strains.
                                Technical Abstract: Influenza A virus (IAV) is widely circulating in the swine population and causes significant economic loss. To combat IAV infection the swine industry utilizes adjuvanted whole inactivated virus (WIV) vaccines. These vaccines can provide sterilizing immunity towards homologous virus but often have limited efficacy against a heterologous infection. Furthermore, the WIV vaccines can have long production times and therefore may not be modified quickly enough for novel emerging strains. There is a need for vaccine platforms that induce mucosal and cell-mediated immunity cross-reactive to heterologous virus that can be produced in a short time frame. Non-replicating adenovirus 5 vector (Ad5) vaccines are one option, as they can be rapidly produced and given intranasally to induce local immunity. Thus, we compared the immunogenicity and efficacy of a single intranasal dose of an Ad5-vectored hemagglutinin (HA) vaccine to traditional intramuscular administration of WIV vaccine. Ad5-HA vaccination induced a mucosal IgA response towards homologous IAV and primed an antigen-specific IFN-gamma response against both challenge viruses. The Ad5-HA vaccine provided protective immunity to homologous challenge and partial protection against heterologous challenge, unlike the WIV vaccine. Nasal shedding was significantly reduced and virus was cleared from the lung by day 5 post-infection following heterologous challenge of Ad5-HA vaccinated pigs. However, the WIV vaccinated pigs displayed vaccine associated enhanced respiratory disease (VAERD) following heterologous challenge, characterized by enhanced macroscopic lung lesions. This study demonstrates that a single intranasal vaccination with an Ad5-HA construct 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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