title: Gp96 SIV Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa.
abstract: The ER-resident chaperone gp96, when released by cell lysis, induces an immunogenic chemokine signature and causes innate immune activation of DC and NK cells. Here we show that intraperitoneal immunization with a genetically engineered, secreted form of gp96, gp96-Ig chaperoning SIV antigens, induces high levels of antigen specific CD8 CTL in the rectal and vaginal mucosa of Rhesus macaques. The frequency of SIV Gag- and SIV Tat-tetramer positive CD8 CTL in the intestinal mucosa reached 30-50% after the third immunization. Tetramer positive CD8 CTL expressed appropriate functional (granzyme B) and migration markers (CD103). The polyepitope specificity of the mucosal CD8 and CD4 response is evident from a strong, multifunctional cytokine response upon stimulation with peptides covering the gag, tat and env proteins. Induction of powerful mucosal effector CD8 CTL responses by cell-based gp96(SIV)-Ig immunization may provide a pathway to the development of safe and effective SIV/HIV vaccines.
authors.affiliation: Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Natasa
authors.initials: N
authors.lastname: Strbo
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kolber
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Louis
authors.initials: L
authors.lastname: Gonzalez
authors.forename: Melvin N
authors.initials: MN
authors.lastname: Doster
authors.forename: Anna
authors.initials: A
authors.lastname: Hryniewicz
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
authors.forename: Eckhard R
authors.initials: ER
authors.lastname: Podack
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D012007:Rectum / Q000276:immunology*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014621:Vagina / Q000276:immunology*
chemical_list: D016207:Cytokines; D000939:Epitopes; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines