title: The ocular conjunctiva as a mucosal immunization route: a profile of the immune response to the model antigen tetanus toxoid.
abstract: BACKGROUND
  In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen.
  
  
  METHODS
  BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 × LD50) of tetanus toxin.
  
  
  RESULTS
  The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFNγ and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p<0.05).
  
  
  CONCLUSIONS
  Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively.
authors: OCUVAC - Center of Ocular Inflammation and Infection, Laura Bassi Centers of Expertise, Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. talin.barisani@meduniwien.ac.at
authors: Talin
authors: T
authors: Barisani-Asenbauer
authors: Aleksandra
authors: A
authors: Inic-Kanada
authors: Sandra
authors: S
authors: Belij
authors: Emilija
authors: E
authors: Marinkovic
authors: Ivana
authors: I
authors: Stojicevic
authors: Jacqueline
authors: J
authors: Montanaro
authors: Elisabeth
authors: E
authors: Stein
authors: Nora
authors: N
authors: Bintner
authors: Marijana
authors: M
authors: Stojanovic
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003228:Conjunctiva / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology*; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000276:immunology; D013363:Submandibular Gland / Q000166:cytology; D013666:Tears / Q000276:immunology; D013744:Tetanus Toxin / Q000633:toxicity; D013745:Tetanus Toxoid / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D013744:Tetanus Toxin; D013745:Tetanus Toxoid
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