Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae

Chanda, A.; Cadena, I. A.; Nazir, J.; Springgay, L.; Rose, I. P.; Abraham, J.; Lin, C.; Saleemi, M. A.; Macintyre, A. N.; DeFilippis, V. R.; Sikora, A. E.

doi:10.64898/2026.11.02.763630

bioRxiv · 10.64898/2026.11.02.763630

Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae

Chanda, A.·Cadena, I. A.·Nazir, J.·Springgay, L.·Rose, I. P.·Abraham, J.·Lin, C.·Saleemi, M. A.·Macintyre, A. N.·DeFilippis, V. R.·Sikora, A. E.

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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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Chanda, A., Cadena, I. A., Nazir, J., Springgay, L., Rose, I. P., Abraham, J., Lin, C., Saleemi, M. A., Macintyre, A. N., DeFilippis, V. R., Sikora, A. E.. 2026-11-03. Mucosal ACP subunit vaccine formulated with a small molecule STING agonist drives protective TH1/TH17 responses and serum bactericidal antibodies against Neisseria gonorrhoeae. https://doi.org/10.64898/2026.11.02.763630

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