AbstractsBiology & Animal Science

The STING Ligand 3’3’-cGAMP Effectively Elicits Mucosal andSystemic Immunity Following Sublingual Immunization

by Tara L Martin




Institution: The Ohio State University
Department:
Year: 2016
Keywords: Veterinary Services; Immunology
Posted: 02/05/2017
Record ID: 2082715
Full text PDF: http://rave.ohiolink.edu/etdc/view?acc_num=osu1461331044


Abstract

Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The currently available vaccine for humans, anthrax vaccine adsorbed (AVA), has a cumbersome immunization schedule and is recommended only for certain high risk adults. The development effective vaccines will depend on selection of appropriate routes of vaccination and appropriate adjuvants. Sublingual immunization is a form of mucosal immunization in which vaccines are applied topically to the floor of the oral cavity. Sublingual vaccines induce antibody production both systemically and at local mucosal sites adjacent to and distant from the sublingual tissues. Stimulator of Interferon Gamma Genes (STING) is a DNA sensor present on the endoplasmic reticulum of mammalian cells. STING has been found to be essential to Type I interferon responses to a variety of pathogens and STING ligands have been shown to act as adjuvants for intranasal and systemic vaccines. 3’3’ cyclic GMP-AMP (3’3’-cGAMP) is a STING ligand of bacterial origin. In this work, mice were immunized by sublingual application of protective antigen (PA) of Bacillus anthracis alone or combined with one of the following experimental adjuvants: cholera toxin (CT), CpG ODN (CpG), or 3’3’-cGAMP. 3’3’-cGAMP effectively elicited systemic IgG and IgA antibody production and these antibodies effectively protected against lethal toxin of Bacillus anthracis. 3’3’-cGAMP also induces secretory IgA (sIgA) production in the saliva and elicited balanced Th1/Th2/Th17 responses. 3’3’-cGAMP significantly increased splenic and bone marrow antibody secreting cells. 3’3’-cGAMP is a promising adjuvant for sublingual immunization, though further studies elucidating both safety and efficacy are warranted. Advisors/Committee Members: Boyaka, Prosper (Advisor).