title: Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa.
abstract: Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral transmission is unknown. To address these questions, we used delay in acute-phase peak viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can have an impact on dissemination of intrarectally administered pathogenic SHIV-ku2 in macaques and that such protection correlates better with mucosal than with systemic CTLs and particularly with levels of high-avidity mucosal CTLs.
authors.affiliation: Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA. belyakov@mail.nih.gov
authors.forename: Igor M
authors.initials: IM
authors.lastname: Belyakov
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.forename: Brian
authors.initials: B
authors.lastname: Kelsall
authors.forename: Dennis
authors.initials: D
authors.lastname: Klinman
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.forename: Michael
authors.initials: M
authors.lastname: Lemon
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Markham
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000628:therapy / Q000635:transmission; D000285:Administration, Rectal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D011212:Poxviridae / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D022223:Vaccines, Subunit