title: Retinoic acid as a vaccine adjuvant enhances CD8+ T cell response and mucosal protection from viral challenge.
abstract: Vaccine-induced memory T cells localized at mucosal sites can provide rapid protection from viral infection. All-trans-retinoic acid (ATRA) has been shown to act physiologically to induce the expression of gut-homing receptors on lymphocytes. We tested whether the administration of exogenous ATRA during a systemic vaccination of mice could enhance the generation of mucosal CD8(+) T cell immunity, which might represent a strategy for establishing better protection from viral infection via mucosal routes. ATRA induced the expression of CCR9 and α4β7 on both mouse and human CD8(+) T cells activated in vitro. The administration of ATRA to mice during in vivo priming with a replication-defective recombinant adenovirus vector expressing the lymphocytic choriomeningitis virus glycoprotein (LCMVgp) (Ad5gp) increased numbers of both effector and memory T cells in intestinal mucosal tissues and showed higher frequencies of systemic central memory-like T cells that exhibited enhanced proliferation during boosting immunization with recombinant modified vaccinia virus Ankara expressing LCMVgp (MVAgp). Mice that received ATRA during Ad5gp vaccination were more resistant to intravaginal challenge by recombinant vaccinia virus expressing LCMVgp (VVgp), reflecting in part stronger T cell recall responses in situ. Thus, ATRA appears to be useful as an adjuvant during vaccination to increase memory T cell responses and protection from viral infection at mucosal sites and may facilitate the development of more effective vaccines against mucosally transmitted pathogens such as HIV.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195-6425, USA.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Tan
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Sande
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Pufnock
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Blattman
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D054388:Receptors, CCR / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*; D014611:Vaccination; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C119309:CC chemokine receptor 9; D006023:Glycoproteins; D011948:Receptors, Antigen, T-Cell; D054388:Receptors, CCR; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D014212:Tretinoin