title: Durable mucosal simian immunodeficiency virus-specific effector memory T lymphocyte responses elicited by recombinant adenovirus vectors in rhesus monkeys.
abstract: The induction of potent and durable cellular immune responses in both peripheral and mucosal tissues may be important for the development of effective vaccines against human immunodeficiency virus type 1 and other pathogens. In particular, effector responses at mucosal surfaces may be critical to respond rapidly to incoming mucosal pathogens. Here we report that intramuscular injection of nonreplicating recombinant adenovirus (rAd) vectors into rhesus monkeys induced remarkably durable simian immunodeficiency virus (SIV)-specific T lymphocyte responses that persisted for over 2 years in both peripheral blood and multiple mucosal tissues, including colorectal, duodenal, and vaginal biopsy specimens, as well as bronchoalveolar lavage fluid. In peripheral blood, SIV-specific T lymphocytes underwent the expected phenotypic evolution from effector memory T cells (T(EM)) to central memory T cells (TCM) following vaccination. In contrast, mucosal SIV-specific T lymphocytes exhibited a persistent and durable T(EM) phenotype that did not evolve over time. These data demonstrate that nonreplicating rAd vectors induce durable and widely distributed effector memory mucosal T lymphocyte responses that are phenotypically distinct from peripheral T lymphocyte responses. Vaccine-elicited T(EM) responses at mucosal surfaces may prove critical for affording protection against invading pathogens at the mucosal portals of entry.
authors.affiliation: Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Hualin
authors.initials: H
authors.lastname: Li
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: Diana
authors.initials: D
authors.lastname: Lynch
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001769:Blood / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004337:Drug Carriers; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D008253:Macaca mulatta; 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; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D004337:Drug Carriers; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic