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- Title
Vaccination with Ad5 Vectors Expands Ad5-Specific CD8<sup>+</sup> T Cells without Altering Memory Phenotype or Functionality.
- Authors
Hutnick, Natalie A.; Carnathan, Diane G.; Dubey, Sheri A.; Cox, Kara S.; Kierstead, Lisa; Makadonas, George; Ratcliffe, Sarah J.; Lasaro, Marcio O.; Robertson, Michael N.; Casimiro, Danilo R.; Ertl, Hildegund C. J.; Betts, Michael R.
- 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. Methodology/Principal Findings: 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.
- Subjects
VACCINATION; T cells; PHENOTYPES; ANTIGENS; IMMUNOGLOBULINS; CYTOMETRY; IMMUNIZATION; LYMPHOCYTES; GENETICS; IMMUNITY
- Publication
PLoS ONE, 2010, Vol 5, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0014385