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
Open Access
- 29 August 2012
- journal article
- Published by American Society for Microbiology in Clinical and Vaccine Immunology
- Vol. 19 (11), 1722-1729
- https://doi.org/10.1128/cvi.00315-12
Abstract
Influenza A virus (IAV) is widely circulating in the swine population and causes significant economic losses. To combat IAV infection, the swine industry utilizes adjuvanted whole inactivated virus (WIV) vaccines, using a prime-boost strategy. These vaccines can provide sterilizing immunity toward homologous virus but often have limited efficacy against a heterologous infection. There is a need for vaccine platforms that induce mucosal and cell-mediated immunity that is cross-reactive to heterologous viruses and can be produced in a short time frame. Nonreplicating adenovirus 5 vector (Ad5) vaccines are one option, as they can be produced rapidly and given intranasally to induce local immunity. Thus, we compared the immunogenicity and efficacy of a single intranasal dose of an Ad5-vectored hemagglutinin (Ad5-HA) vaccine to those of a traditional intramuscular administration of WIV vaccine. Ad5-HA vaccination induced a mucosal IgA response toward homologous IAV and primed an antigen-specific gamma interferon (IFN-γ) 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 postinfection 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 from homologous challenge and partial protection from heterologous challenge, as opposed to VAERD, which can occur with adjuvanted WIV vaccines.Keywords
This publication has 36 references indexed in Scilit:
- DNA Vaccination Elicits Protective Immune Responses against Pandemic and Classic Swine Influenza Viruses in PigsClinical and Vaccine Immunology, 2011
- Lowering the Threshold of Lung Innate Immune Cell Activation Alters Susceptibility to Secondary Bacterial SuperinfectionThe Journal of Infectious Diseases, 2011
- Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in miceJCI Insight, 2011
- Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 VirusesPLOS ONE, 2010
- A Candidate H1N1 Pandemic Influenza Vaccine Elicits Protective Immunity in MicePLOS ONE, 2010
- Memory CD4+ T cells induce innate responses independently of pathogenNature Medicine, 2010
- Pandemic (H1N1) 2009 Outbreak on Pig Farm, ArgentinaEmerging Infectious Diseases, 2010
- Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccinesBlood, 2007
- The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccinationVeterinary Immunology and Immunopathology, 2006
- Genetic relationships, serological cross-reaction and cross-protection between H1N2 and other influenza A virus subtypes endemic in European pigsVirus Research, 2004