title: Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice.
abstract: The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa; however, there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants, we have assessed whether the B-cell-activating cytokines APRIL, BAFF and TSLP enhance humoral immune responses to HIV-1 gp140. Following intranasal immunisation, TSLP but not APRIL or BAFF induced strong humoral responses both in serum and mucosa. The adjuvant effect of TSLP on humoral responses was similar to that of cholera toxin (CT). The use of TSLP as an adjuvant skewed both the cellular and humoral immune responses towards Th2 cells. This is the first time that TSLP has been demonstrated to have a positive effect as a mucosal adjuvant, and specifically to promote mucosal and systemic responses to HIV gp140.
authors: Centre for Infection and Immunity, Division of Clinical Science, St. George's University of London, Cranmer Terrace, London, UK.
authors: Griet A
authors: GA
authors: Van Roey
authors: Mauricio A
authors: MA
authors: Arias
authors: John S
authors: JS
authors: Tregoning
authors: George
authors: G
authors: Rowe
authors: Robin J
authors: RJ
authors: Shattock
mesh_terms: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000008:administration & dosage / Q000009:adverse effects; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage* / Q000009:adverse effects; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000008:administration & dosage / Q000009:adverse effects; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D053264:B-Cell Activating Factor; D016207:Cytokines; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D000094632:Thymic Stromal Lymphopoietin