title: Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins.
abstract: Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in infants and a high priority for vaccine development. We previously reported that RSV virus-like particles (VLPs) expressing either the fusion (F) or attachment (G) glycoprotein could confer protection against RSV challenge in BALB/c mice. Here, we tested the hypothesis that RSV VLP vaccine efficacy can be enhanced by mixing RSV VLP F and RSV VLP G, and we analyzed host responses to these RSV VLPs. Mice were immunized with VLP F, VLP G, or VLP F+VLP G. Lung viral loads in BALB/c mice following RSV strain A2-line19F challenge were lower in mice vaccinated with RSV VLP F+VLP G compared to VLP F- or VLP G-vaccinated mice. Vaccination with VLP F or VLP F+VLP G induced similar levels of neutralizing antibodies. The enhanced protection against RSV challenge induced by vaccination with RSV VLP F+VLP G correlated with CD8 T cells producing T helper type 1 cytokines. VLP G vaccination alone followed by challenge resulted in immunopathology similar to formalin-inactivated RSV vaccination and RSV challenge. Taken together, mixed VLP F+VLP G provided a high level of protection against RSV without vaccine-induced immunopathology, but VLP G vaccination enhanced disease when used alone.
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA.
authors.forename: Sujin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, Republic of Korea; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
authors.affiliation: Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
authors.forename: Youngman
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Pathology, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: 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
authors.affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: martin.moore@emory.edu.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins
keywords: Lung pathology; RSV attachment glyco (G) protein; RSV fusion (F) protein; Respiratory syncytial virus; Virus like particle (VLP)