title: Vaccination with Ad5 vectors expands Ad5-specific CD8 T cells without altering memory phenotype or functionality.
abstract: BACKGROUND
  Adenoviral (Ad) vaccine vectors represent both a vehicle to present a novel antigen to the immune system as well as restimulation of immune responses against the Ad vector itself. To what degree Ad-specific CD8(+) T cells are restimulated by Ad vector vaccination is unclear, although such knowledge would be important as vector-specific CD8(+) T cell expansion could potentially further limit Ad vaccine efficacy beyond Ad-specific neutralizing antibody alone.
  
  
  RESULTS
  Here we addressed this issue by measuring human Adenovirus serotype 5 (Ad5)-specific CD8(+) T cells in recipients of the Merck Ad5 HIV-1 vaccine vector before, during, and after vaccination by multicolor flow cytometry. Ad5-specific CD8(+) T-cells were detectable in 95% of subjects prior to vaccination, and displayed primarily an effector-type functional profile and phenotype. Peripheral blood Ad5-specific CD8(+) T-cell numbers expanded after Ad5-HIV vaccination in all subjects, but differential expansion kinetics were noted in some baseline Ad5-neutralizing antibody (Ad5 nAb) seronegative subjects compared to baseline Ad5 nAb seropositive subjects. However, in neither group did vaccination alter polyfunctionality, mucosal targeting marker expression, or memory phenotype of Ad5-specific CD8(+) T-cells.
  
  
  CONCLUSIONS
  These data indicate that repeat Ad5-vector administration in humans expands Ad5-specific CD8(+) T-cells without overtly affecting their functional capacity or phenotypic properties. This is a secondary analysis of samples collected during the 016 trial. Results of the Merck 016 trial safety and immunogenicity have been previously published in the journal of clinical infectious diseases [1].
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00849680[http://www.clinicaltrials.gov/show/NCT00849680].
authors.affiliation: Department of Microbiology and Center for AIDS Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Hutnick
authors.forename: Diane G
authors.initials: DG
authors.lastname: Carnathan
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Dubey
authors.forename: Kara S
authors.initials: KS
authors.lastname: Cox
authors.forename: Lisa
authors.initials: L
authors.lastname: Kierstead
authors.forename: George
authors.initials: G
authors.lastname: Makadonas
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ratcliffe
authors.forename: Marcio O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D016466:CHO Cells; D002986:Clinical Trials as Topic; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008954:Models, Biological; D010641:Phenotype; D013997:Time Factors
chemical_list: D016915:AIDS Vaccines