title: Adenovirus serotype 26 and 35 vectors induce simian immunodeficiency virus-specific T lymphocyte responses in foreskin in rhesus monkeys.
abstract: Foreskin is the principal site of heterosexual HIV-1 infection in men. However, little is known about HIV-1-specific immune responses or inflammation in foreskin. To the best of our knowledge, no previous studies have assessed immune responses to candidate HIV-1 vaccines in foreskin. Using the rhesus monkey model, we show that intramuscular immunization with adenovirus serotype 26 and 35 vectors expressing SIV antigens elicited durable SIV Gag-specific CD4(+) and CD8(+) T cell responses in foreskin that were detectable for more than 1 year following vaccination. Gag-specific CD4(+) and CD8(+) T cells were also detectable in foreskin of SIV- and SHIV-infected animals and were at least comparable in magnitude to those in peripheral blood. However, unlike peripheral blood T cells, the majority of foreskin T cells exhibited transitional memory or effector memory phenotype and expressed higher levels of the activation markers CD69, HLA-DR, and CCR5, although vaccination did not further enhance foreskin CD4(+) T cell activation. These findings suggest that systemic vaccination strategies can elicit potentially important SIV-specific cellular immunity in foreskin. Further characterization of vaccine-elicited immune responses and inflammation in foreskin is warranted.
  
  
  OBJECTIVE
  We demonstrate here the induction of SIV-specific cellular immune responses in foreskin by adenovirus serotype 26 and 35 vaccine vectors. Foreskin T cells were more activated than peripheral blood T cells, but foreskin T cells were not further activated by vaccination. These findings suggest that alternative serotype adenovirus vectors induce potentially important immune responses in foreskin.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Balandya
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.forename: Matthew
authors.initials: M
authors.lastname: Beck
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Hualin
authors.initials: H
authors.lastname: Li
authors.forename: Erica
authors.initials: E
authors.lastname: Borducchi
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Smith
authors.forename: Crystal
authors.initials: C
authors.lastname: Cabral
authors.forename: Kelly
authors.initials: K
authors.lastname: Stanley
authors.forename: Lori F
authors.initials: LF
authors.lastname: Maxfield
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004337:Drug Carriers; D052816:Foreskin / Q000276:immunology*; D005822:Genetic Vectors; D016130:Immunophenotyping; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D008297:Male; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D018449:SAIDS Vaccines