title: A novel inactivated intranasal respiratory syncytial virus vaccine promotes viral clearance without Th2 associated vaccine-enhanced disease.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in young children worldwide, and no vaccine is currently available. Inactivated RSV vaccines tested in the 1960's led to vaccine-enhanced disease upon viral challenge, which has undermined RSV vaccine development. RSV infection is increasingly being recognized as an important pathogen in the elderly, as well as other individuals with compromised pulmonary immunity. A safe and effective inactivated RSV vaccine would be of tremendous therapeutic benefit to many of these populations.
  
  
  RESULTS
  In these preclinical studies, a mouse model was utilized to assess the efficacy of a novel, nanoemulsion-adjuvanted, inactivated mucosal RSV vaccine. Our results demonstrate that NE-RSV immunization induced durable, RSV-specific humoral responses, both systemically and in the lungs. Vaccinated mice exhibited increased protection against subsequent live viral challenge, which was associated with an enhanced Th1/Th17 response. In these studies, NE-RSV vaccinated mice displayed no evidence of Th2 mediated immunopotentiation, as has been previously described for other inactivated RSV vaccines.
  
  
  CONCLUSIONS
  These studies indicate that nanoemulsion-based inactivated RSV vaccination can augment viral-specific immunity, decrease mucus production and increase viral clearance, without evidence of Th2 immune mediated pathology.
authors.affiliation: Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, United States of America.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Lindell
authors.forename: Susan B
authors.initials: SB
authors.lastname: Morris
authors.forename: Maria P
authors.initials: MP
authors.lastname: White
authors.forename: Lara E
authors.initials: LE
authors.lastname: Kallal
authors.forename: Phillip K
authors.initials: PK
authors.lastname: Lundy
authors.forename: Tarek
authors.initials: T
authors.lastname: Hamouda
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004655:Emulsions; D004802:Eosinophilia / Q000150:complications / Q000276:immunology; D007109:Immunity; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013045:Species Specificity; D018418:Th2 Cells / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology*; D019562:Viral Load / Q000276:immunology; D038301:Virus Inactivation
chemical_list: D016207:Cytokines; D004655:Emulsions; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated