Gonorrhea is a genital tract infection caused by Neisseria gonorrhoeae, which can be acquired repeatedlyand does not naturally induce a state of specific protective immunity against reinfection. Despite publichealth measures, gonorrhea persists at an unacceptably high frequency, and there is no vaccine againstit. The continuing emergence of antibiotic resistance threatens to render gonorrhea untreatable. Ourfindings have revealed that N. gonorrhoeae subverts the immune system for its own benefit by inducinghigh levels of the immuno-regulatory cytokine, interleukin-10 (IL-10). Using the established murine modelof vaginal gonococcal infection, we propose to investigate a novel strategy of vaccination against N.gonorrhoeae, exploiting neutralizing antibody against IL-10 encapsulated in biodegradable micro-particles(GneXa10®) as adjuvant. As vaccine antigen, outer membrane vesicles (OMV) derived from a double-mutant (dm) strain of N. gonorrhoeae, designed to reduce adverse responses to administration in humans,will be used. We will determine the role of serum and mucosal antibody and T-cell cytokine responses tointra-nasal (i.n.) immunization with dmOMV plus GneXa10®, in resistance to challenge infection with bothhomologous and heterologous strains. Persistence of immunity and recall of memory responses atincreasing time intervals after immunization will be evaluated. Functional antibodies active against N.gonorrhoeae will be assessed in vitro. This work will provide proof-of-principle for a vaccine based ongonococcal dmOMVs and GneXa10®. Future SBIR phase II studies will further elucidate mechanisms ofcross-protection against diverse strains of N. gonorrhoeae, and validate the expected applicability ofscaled-up vaccine development, evaluating yield, bioactivity, batch-to-batch consistency, and shelfstability. This proposal is part of our company's response to the CDC's and WHO's calls for developmentof novel vaccine approaches in the face of the public health threat posed by antibiotic-resistant N.gonorrhoeae.
Public Health Relevance Statement: NARRATIVE (PUBLIC HEALTH RELEVANCE STATEMENT)
Gonorrhea is the second-most-frequent, notifiable infectious disease in the United States; the Centers for
Disease Control report >580,000 cases annually, and world-wide incidence is estimated at 87 million new
infections per year. No vaccine is available and the emergence of multiple-drug-resistant strains now
raises serious and urgent concerns over future treatment options. This proposal seeks to develop a novel
strategy for vaccination against gonorrhea, utilizing outer membrane vesicles from a double-mutant strain
of Neisseria gonorrhoeae as antigen and a novel adjuvant that generates protective immunity against
infection.
Project Terms: <7S Gamma Globulin>
