Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae
- 1Oregon State University
Abstract
STING agonists are emerging vaccine adjuvants; however, only cyclic dinucleotides (low permeability and stability) have been tested against pathogenic bacteria. We examined diABZI, a non-nucleotide STING agonist active in human and murine orthologs, combined with the Neisseria gonorrhoeae (Ng) Adhesin Complex Protein, a conserved adhesin and human lysozyme C inhibitor, as a gonococcal vaccine. Intranasal administration of recombinant ACP (rACP)+diABZI accelerated gonococcal clearance, in contrast to rACP or rACP+CpG+MPLA, despite comparable antibody responses. While both diABZI and CpG+MPLA induced TH1, diABZI also induced TH17 polarization. Peptide mapping localized the immunodominant T cell epitopes to the ACP-lysozyme C interface. rACP+diABZI elicited higher human serum bactericidal activity (hSBA), that correlated with Ng clearance, and antibodies that reversed human lysozyme C inhibition and interfered with Ng adhesion and invasion in 3D human vaginal/urethral mucosal models. Passive serum transfer did not recapitulate protection, implicating mucosal antibodies and cellular immunity over circulating IgG.
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BibTeX
@misc{chanda2026mucosal,
title = {{Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae}},
author = {A. Chanda and I. A. Cadena and J. Nazir and L. Springgay and I. P. Rose and J. Abraham and C. Lin and M. A. Saleemi and A. N. Macintyre and V. R. DeFilippis and A. E. Sikora},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.763630},
url = {https://www.biorxiv.org/content/10.64898/2026.11.02.763630v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae
AU - A. Chanda
AU - I. A. Cadena
AU - J. Nazir
AU - L. Springgay
AU - I. P. Rose
AU - J. Abraham
AU - C. Lin
AU - M. A. Saleemi
AU - A. N. Macintyre
AU - V. R. DeFilippis
AU - A. E. Sikora
PY - 2026
DA - 2026/11/02
PB - bioRxiv
DO - 10.64898/2026.11.02.763630
UR - https://www.biorxiv.org/content/10.64898/2026.11.02.763630v1
AB - STING agonists are emerging vaccine adjuvants; however, only cyclic dinucleotides (low permeability and stability) have been tested against pathogenic bacteria. We examined diABZI, a non-nucleotide STING agonist active in human and murine orthologs, combined with the Neisseria gonorrhoeae (Ng) Adhesin Complex Protein, a conserved adhesin and human lysozyme C inhibitor, as a gonococcal vaccine. Intranasal administration of recombinant ACP (rACP)+diABZI accelerated gonococcal clearance, in contrast to rACP or rACP+CpG+MPLA, despite comparable antibody responses. While both diABZI and CpG+MPLA induced TH1, diABZI also induced TH17 polarization. Peptide mapping localized the immunodominant T cell epitopes to the ACP-lysozyme C interface. rACP+diABZI elicited higher human serum bactericidal activity (hSBA), that correlated with Ng clearance, and antibodies that reversed human lysozyme C inhibition and interfered with Ng adhesion and invasion in 3D human vaginal/urethral mucosal models. Passive serum transfer did not recapitulate protection, implicating mucosal antibodies and cellular immunity over circulating IgG.
ER -