6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Sublingual targeting of STING with 3′3′-cGAMP promotes systemic and mucosal immunity against anthrax toxins

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The current human anthrax vaccine, anthrax vaccine adsorbed (AVA), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. Bacterial enterotoxins, which stimulate production of the cyclic nucleotide cAMP are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. We investigated whether cyclic dinucleotides that target Stimulator of Interferon Gamma Genes (STING) in mammalian cells could represent an alternative to bacterial enterotoxins as adjuvant for sublingual immunization and promotion of mucosal immunity and secretory IgA responses in addition to systemic immunity. We found that sublingual immunization of mice with Bacillus anthracis protective antigen (PA) and the STING ligand 3′3′-cGAMP promotes PA-specific serum IgG Ab responses of the same magnitude as those induced after immunization with PA and the experimental adjuvants cholera toxin (CT). Interestingly, this STING ligand also promoted serum anti-PA IgA and IgA-producing cells in the bone marrow. Furthermore, the saliva of mice immunized with the STING ligand exhibited similar levels of PA-specific IgA Abs as groups immunized with CT as adjuvant. The adjuvant activity of 3′3′-cGAMP was associated with mixed Th1, Th2, and Th17 responses. This STING ligand also induced rapid IFN-β and IL-10 responses in sublingual tissues and cervical lymph nodes, and TGF-β responses in the cervical lymph nodes, which could contribute to promoting IgA responses after sublingual immunization.

          Related collections

          Author and article information

          Journal
          8406899
          7945
          Vaccine
          Vaccine
          Vaccine
          0264-410X
          1873-2518
          13 April 2017
          24 March 2017
          25 April 2017
          25 April 2018
          : 35
          : 18
          : 2511-2519
          Affiliations
          [1 ]Department of Veterinary Biosciences, The Ohio State University, Columbus, OH
          Author notes
          Correspondence: Dr. Prosper N. Boyaka, The Ohio State University, Dept. of Veterinary Biosciences, VMAB, 1900 Coffey Road, Columbus, OH 43210. Telephone # (614) 247-4671 Fax #: (614) 292-6473. boyaka.1@ 123456osu.edu
          Article
          PMC5719503 PMC5719503 5719503 nihpa862783
          10.1016/j.vaccine.2017.02.064
          5719503
          28343781
          7e0a5aa5-89d6-45b8-b00a-ca38ffb8dcc9
          Categories
          Article

          Comments

          Comment on this article