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2017 ; 35
(18
): 2511-2519
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Sublingual targeting of STING with 3 3 -cGAMP promotes systemic and mucosal
immunity against anthrax toxins
#MMPMID28343781
Martin TL
; Jee J
; Kim E
; Steiner HE
; Cormet-Boyaka E
; Boyaka PN
Vaccine
2017[Apr]; 35
(18
): 2511-2519
PMID28343781
show ga
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 adjuvant 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-? and IL-10 responses in
sublingual tissues and cervical lymph nodes, and TGF-? responses in the cervical
lymph nodes, which could contribute to promoting IgA responses after sublingual
immunization.