title: Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses.
abstract: The induction of mucosal immune responses in the genital tract may be important for increasing the effectiveness of vaccines for sexually transmitted infections (STIs). In this study, we asked whether direct immunization of the mouse genital tract with a non-replicating virus-like particle (VLP)-based vaccine could induce local mucosal as well as systemic antibody responses. Using VLPs derived from two bacteriophages, Qβ and PP7, and from a mammalian virus that normally infects the genital tract, human papillomavirus (HPV), we show that intravaginal aerosol administration of VLPs can induce high titer IgG and IgA antibodies in the female genital tract as well as IgG in the sera. Using a mouse model for HPV infection, we show that intravaginal immunization with either HPV type 16 VLPs or with PP7 bacteriophage VLPs displaying a peptide derived from the HPV minor capsid protein L2 could protect mice from genital infection with an HPV16 pseudovirus. These results provide a general method for inducing genital mucosal and systemic antibody responses using VLP-based immunogens.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, United States.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Hunter
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Tumban
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dziduszko
authors.forename: Bryce
authors.initials: B
authors.lastname: Chackerian
mesh_terms: D000282:Administration, Intravaginal; D000336:Aerosols; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D000917:Antibody Formation; D036022:Capsid Proteins / Q000276:immunology; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology* / Q000517:prevention & control; D052162:Human papillomavirus 16 / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000276:immunology; D014771:Virion / Q000276:immunology
chemical_list: D000336:Aerosols; D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle