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

A new vaccine composed of Neisseria gonorrhoeae adhesin complex protein (ACP) and a small molecule STING agonist called diABZI demonstrated promising results in driving protective TH1 and TH17 immune responses, as well as serum bactericidal antibodies, against the pathogenic bacterium.

STING agonists have been explored as vaccine adjuvants, but only low-permeability and low-stability cyclic dinucleotides have been tested against bacteria. The researchers investigated diABZI, a non-nucleotide STING agonist that is active in both human and murine orthologs, in combination with ACP. They administered this combination intranasally in mice.

The results showed that the rACP+diABZI combination accelerated the clearance of gonococcal infection, unlike rACP or rACP+CpG+MPLA, even though antibody responses were similar among the groups. Both diABZI and CpG+MPLA induced TH1 responses, but diABZI also stimulated TH17 polarization. The researchers identified the immunodominant T cell epitopes in the ACP-lysozyme C interface through peptide mapping.

The rACP+diABZI vaccine elicited higher levels of human serum bactericidal activity (hSBA), which correlated with the clearance of Neisseria gonorrhoeae, and produced antibodies that could reverse human lysozyme C inhibition while interfering with the bacterium's adhesion and invasion in 3D human vaginal/urethral mucosal models.

However, passive serum transfer did not replicate the protective effect, suggesting that mucosal antibodies and cellular immunity are more crucial than circulating IgG for protection against gonorrhea.