title: Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus.
abstract: Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate.
authors.affiliation: The Pirbright Institute, Surrey GU24 0NF, United Kingdom;
authors.forename: Sophie B
authors.initials: SB
authors.lastname: Morgan
authors.affiliation: The Pirbright Institute, Surrey GU24 0NF, United Kingdom;
authors.forename: Johanneke D
authors.identifier: 0000-0001-8764-4156
authors.initials: JD
authors.lastname: Hemmink
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol BS40 5DU, United Kingdom;
authors.forename: Emily
authors.identifier: 0000-0002-1213-3260
authors.initials: E
authors.lastname: Porter
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol BS40 5DU, United Kingdom;
authors.forename: Ross
authors.identifier: 0000-0001-9663-4486
authors.initials: R
authors.lastname: Harley
authors.affiliation: The Pirbright Institute, Surrey GU24 0NF, United Kingdom;
authors.forename: Holly
authors.initials: H
authors.lastname: Shelton
authors.affiliation: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom;
authors.forename: Mario
authors.initials: M
authors.lastname: Aramouni
authors.affiliation: Virology Department, Animal and Plant Health Agency, Weybridge, Surrey KT15 3NB, United Kingdom; and.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Everett
authors.affiliation: Virology Department, Animal and Plant Health Agency, Weybridge, Surrey KT15 3NB, United Kingdom; and.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Brookes
authors.affiliation: School of Veterinary Sciences, University of Bristol, Bristol BS40 5DU, United Kingdom;
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Townsend
authors.affiliation: The Pirbright Institute, Surrey GU24 0NF, United Kingdom;
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
authors.affiliation: The Pirbright Institute, Surrey GU24 0NF, United Kingdom; elma.tchilian@pirbright.ac.uk.
authors.forename: Elma
authors.initials: E
authors.lastname: Tchilian
mesh_terms: D000336:Aerosols; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D009666:Nose / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D058873:Pandemics / Q000517:prevention & control; D034421:Sus scrofa; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
chemical_list: D000336:Aerosols; D057134:Antibodies, Neutralizing; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D007371:Interferon-gamma