Gonorrhea Subunit Vaccine

Background of Invention

Each year witnesses roughly 78 million new gonorrhea infections [etiologic agent Neisseria gonorrhoeae (Ng)] worldwide. While often asymptomatic (particularly in females), untreated infection can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and increased transmission/acquisition of HIV. Although antimicrobials have been the standard treatment for gonorrhea, Ng has developed resistance to all antimicrobials used in empiric treatment. WHO, CDC, other public health organizations, and researchers have raised an urgent call for an effective gonorrhea vaccine, noting that this may be the only sustainable solution to reduce the disease burden and control its global spread. Developing rMetQ-CpG vaccine can contribute to generation of protective gonorrhea vaccine.

Technology Description

A gonorrhea vaccine based on a MetQ protein combined with a K-type CpG oligodeoxynucleotide, which induces a strong immune response. The strong immune response is achieved with administration via subcutaneous prime followed by 3 intranasal boosts. There is potential to use the formulation as part of a multivalent gonorrhea vaccine or as a monovalent vaccine. To assess whether immunization with MetQ induces a protective immune response, we conducted large scale experiments in biological replicates in which groups of 20 BALB/c mice were given rMetQ formulated with CpG by the subcutaneous prime, followed by three intranasal boosts. Control groups consisted of mice given adjuvant alone or PBS using the same immunization routes and time points. The MetQ-CpG subunit vaccine elicited high serum antibody titers and sera as well as mucosal secretions that specifically recognized MetQ in immunoblotting against purified MetQ antigen and Neisseria gonorrhoeae (Ng) cell envelope proteins. Significantly higher titers of total IgG, IgG1, Ig2a, and IgA were detected in the sera from mice immunized with rMetQ-CpG compared to both control groups. Finally combined biological replicate challenge experiments demonstrated that mice immunized with rMetQ-CpG significantly faster cleared gonococcal infection compared to unimmunized mice (p<0.0001) and adjuvant control (p=0.0013). Seventy-five and 90% of mice immunized with MetQ cleared infection by day 5 and 7, respectively in contrast to 43% and 65% in the CpG alone group and 10% and 38% in the PBS control group. We conclude that MetQ formulated with CpG induces a protective immune response that results in accelerated Ng clearance from the murine lower genital tract and thus represent subunit vaccine for further gonorrhea vaccine development.

Benefits