title: Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances clearance of respiratory syncytial virus in a mouse model.
abstract: Respiratory Syncytial Virus (RSV) is a ubiquitous virus that infects almost all people by age two and is a major source of respiratory illness in infants, the elderly and others with compromised immune systems. Currently there is no available vaccine. Prior efforts using formalin-inactivated RSV (FI-RSV) were associated with enhanced respiratory disease upon viral exposure following clinical vaccine trials. Several researchers and pharmaceutical companies have utilized vector-associated live attenuated RSV vaccines in pre-clinical and clinical studies. Another attractive approach, however, is a subunit vaccine which would be easier to produce and quality control. Our group has previously demonstrated in a murine model of infection that intranasal immunization with nanoemulsion-inactivated and adjuvanted RSV induces humoral and cellular immune responses, resulting in protection against RSV infection. The present studies characterize the immune responses elicited by intranasal RSV F protein adjuvanted with nanoemulsion. Intranasal application of nanoemulsion adjuvanted F protein induced a rapid and robust systemic and mucosal antibody response, as well as protection against subsequent RSV challenge. Importantly, RSV challenge in immunized animals did not elicit airway hyper-reactivity, a Th2-skewed immune response or immunopathology associated with hypersensitivity reactions with formalin-inactivated vaccine. These results suggest that RSV F protein adjuvanted with nanoemulsion may be a good mucosal vaccine candidate. Formulating RSV F protein in nanoemulsion creates a well-defined and well-controlled vaccine that can be delivered intranasally to induce T cell mediated immunity without inducing enhanced disease associated with the mouse model of FI-RSV vaccination and infection.
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences; University of Michigan Medical School; Ann Arbor, MI USA.
authors: Crystal
authors: C
authors: Passmore
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences; University of Michigan Medical School; Ann Arbor, MI USA; The Unit for Laboratory Animal Medicine; Medical School; University of Michigan; Ann Arbor, MI USA.
authors: Paul E
authors: PE
authors: Makidon
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences; University of Michigan Medical School; Ann Arbor, MI USA.
authors: Jessica J
authors: JJ
authors: O'Konek
authors: University of Michigan Medical School; Ann Arbor, MI USA.
authors: Joseph A
authors: JA
authors: Zahn
authors: NanoBio Corporation; Ann Arbor, MI USA.
authors: Jessie
authors: J
authors: Pannu
authors: NanoBio Corporation; Ann Arbor, MI USA.
authors: Tarek
authors: T
authors: Hamouda
authors: NanoBio Corporation; Ann Arbor, MI USA.
authors: Vira
authors: V
authors: Bitko
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences; University of Michigan Medical School; Ann Arbor, MI USA; Department of Immunology of Infectious Diseases; Ludwik Hirszfeld Institute of Immunology and Experimental Therapy; Polish Academy of Sciences; Wroclaw, Poland.
authors: Andrzej
authors: A
authors: Myc
authors: Department of Pathology; University of Michigan; Ann Arbor, MI USA.
authors: Nicolas W
authors: NW
authors: Lukacs
authors: NanoBio Corporation; Ann Arbor, MI USA.
authors: Ali
authors: A
authors: Fattom
authors: Michigan Nanotechnology Institute for Medicine and Biological Sciences; University of Michigan Medical School; Ann Arbor, MI USA.
authors: James R
authors: JR
authors: Baker
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001769:Blood / Q000276:immunology; D004195:Disease Models, Animal; D004655:Emulsions / Q000008:administration & dosage; D005260:Female; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004655:Emulsions; C526850:F protein, human respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D014760:Viral Fusion Proteins
keywords: F-protein; RSV vaccine; adjuvant; intranasal vaccination; nanoemulsion