title: Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats.
abstract: Vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (RSV). This study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (VLP) vaccines containing RSV F (F VLP), G (G VLP), or F and G proteins (FG VLP) in cotton rats. RSV specific antibodies were effectively induced by vaccination of cotton rats with F VLP or FG VLP vaccines. After challenge, lung RSV clearance was observed with RSV F, G, FG VLP, and formalin inactivated RSV (FI-RSV) vaccines. Upon RSV infection, cotton rats with RSV VLP vaccines were protected against airway hyper-responsiveness and weight loss, which are different from FI-RSV vaccination exhibiting vaccine-enhanced disease of airway obstruction, weight loss, and severe histopathology with eosinophilia and mucus production. FG VLP and F VLP vaccines did not cause pulmonary inflammation whereas G VLP induced moderate lung inflammation with eosinophilia and mucus production. In particular, F VLP and FG VLP vaccines were found to be effective in inducing antibody secreting cell responses in bone marrow and lymphoid organs as well as avoiding the induction of T helper type 2 cytokines. These results provide further evidence to develop a safe RSV vaccine based on VLP platforms.
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Ki-Hye
authors.initials: KH
authors.lastname: Kim
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Youri
authors.initials: Y
authors.lastname: Lee
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Lee
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Ko
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: SooJin
authors.initials: S
authors.lastname: Park
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.|b National Institute of Biological Resources , Incheon , South Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Byung-Cheol
authors.initials: BC
authors.lastname: Lee
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Kwon
authors.affiliation: c Department of Pediatrics , Emory University , Atlanta , GA , USA.|d Children's Healthcare of Atlanta , Atlanta , GA , USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.affiliation: a Center for Inflammation, Immunity & Infection , Institute for Biomedical Sciences, Georgia State University , Atlanta , GA , USA.
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood; D000071497:Immunogenicity, Vaccine; D008168:Lung / Q000473:pathology; D011014:Pneumonia; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D016205:Sigmodontinae; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C526850:F protein, human respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins
keywords: cotton rats; respiratory syncytial virus; virus-like particle