title: Vaccination of pigs against swine influenza viruses by using an NS1-truncated modified live-virus vaccine.
abstract: Swine influenza viruses (SIV) naturally infect pigs and can be transmitted to humans. In the pig, genetic reassortment to create novel influenza subtypes by mixing avian, human, and swine influenza viruses is possible. An SIV vaccine inducing cross-protective immunity between different subtypes and strains circulating in pigs is highly desirable. Previously, we have shown that an H3N2 SIV (A/swine/Texas/4199-2/98 [TX98]) containing a deleted NS1 gene expressing a truncated NS1 protein of 126 amino acids, NS1black triangle126, was attenuated in swine. In this study, 4-week-old pigs were vaccinated with the TX98 NS1black triangle126 modified live virus (MLV). Ten days after boosting, pigs were challenged with wild-type homologous H3N2 or heterosubtypic H1N1 SIV and sacrificed 5 days later. The MLV was highly attenuated and completely protected against challenge with the homologous virus. Vaccinated pigs challenged with the heterosubtypic H1N1 virus demonstrated macroscopic lung lesions similar to those of the unvaccinated H1N1 control pigs. Remarkably, vaccinated pigs challenged with the H1N1 SIV had significantly lower microscopic lung lesions and less virus shedding from the respiratory tract than did unvaccinated, H1N1-challenged pigs. All vaccinated pigs developed significant levels of hemagglutination inhibition and enzyme-linked immunosorbent assay titers in serum and mucosal immunoglobulin A antibodies against H3N2 SIV antigens. Vaccinated pigs were seronegative for NS1, indicating the potential use of the TX98 NS1black triangle126 MLV as a vaccine to differentiate infected from vaccinated animals.
authors.affiliation: Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 2300 Dayton Ave. B-15, Ames, IA 50010, USA. jricht@nadc.ars.usda.gov
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Richt
authors.forename: Porntippa
authors.initials: P
authors.lastname: Lekcharoensuk
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Lager
authors.forename: Amy L
authors.initials: AL
authors.lastname: Vincent
authors.forename: Christina M
authors.initials: CM
authors.lastname: Loiacono
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Janke
authors.forename: Wai-Hong
authors.initials: WH
authors.lastname: Wu
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Yoon
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Alicia
authors.initials: A
authors.lastname: Solórzano
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006385:Hemagglutination Inhibition Tests; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000473:pathology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D020545:Respiratory Mucosa / Q000276:immunology; D017384:Sequence Deletion; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; C085820:INS1 protein, influenza virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins