title: Both mucosal and systemic routes of immunization with the live, attenuated NYVAC/simian immunodeficiency virus SIV(gpe) recombinant vaccine result in gag-specific CD8(+) T-cell responses in mucosal tissues of macaques.
abstract: As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A(*)01 molecule to assess the capacity of the highly attenuated poxvirus NYVAC/simian immunodeficiency virus (SIV) SIV(gpe) vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIV(mac251) by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NYVAC/SIV(gpe) and the anamnestic response to SIV(mac251) at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIV(mac) Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigen-specific CD8(+) T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIV(mac251) challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8(+) T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes.
authors.affiliation: Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Liljana
authors.initials: L
authors.lastname: Stevceva
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Brian
authors.initials: B
authors.lastname: Kelsall
authors.forename: Janos
authors.initials: J
authors.lastname: Nacsa
authors.forename: Jim
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D000281:Administration, Intranasal; D000285:Administration, Rectal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology; D007273:Injections, Intramuscular; D008251:Macaca; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014616:Vaccinia virus; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D015683:Gene Products, gag; D016056:Immunodominant Epitopes; C078787:NYVAC vaccine; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines