Efficacy of Immunization With 4C-MenB in Preventing Experimental Urethral Infection With Neisseria Gonorrhoeae

Inclusion Criteria:

Participants must meet all the inclusion criteria to participate in the study.

• Assigned male at birth and now ≥ 18 and < 36 years old

• No history of prior Neisseria meningitidis serogroup B (MenB) vaccination

• Able and willing to be located easily by providing street address and telephonenumber (land line and/or cell phone number)

• Willingness to provide written informed consent

• Informed consent obtained and signed

• Able and willing to attend all study visits

• Able and willing to abstain from all sexual activity involving contact with theparticipant's penis, urine, or semen and a person other than the participant duringexperimental gonococcal infection phase until the follow-up test for gonorrhea isnegative

• Able and willing to abstain from scheduled immunizations other than those providedthrough the study, between enrollment and completion of Ng challenge.

• No clinically significant abnormalities on physical exam

• Urinalysis: leukocyte esterase and WBC values within normal limits

• 50% complement hemolytic activity (CH50) within normal limits (WNL)

• Negative HIV and syphilis test results at the screening visit

• Denies history of bleeding diathesis

• Denies history of seizures (due to reports of seizures with ciprofloxacin), historyof childhood febrile seizure acceptable

• Denies history of cancer, except basal cell carcinoma of the skin >5 years ago

• Denies current drug abuse that would interfere with study activities

• Denies history of penile, urethral, prostate, testis and associated structuressurgery (varicocele repair, vasectomy, and vasectomy repair are acceptable ifgreater than 1 year prior to enrollment)

Exclusion Criteria:

Participants meeting any of the exclusion criteria at initial screening and screening prior to Ng challenge will be excluded from study participation. If the results of Complete blood count (CBC), serum alanine transaminase (ALT), serum creatinine, or urinalysis obtained at initial screening are outside acceptable limits, and the clinician judges the deviation unlikely to be clinically relevant, one-time repeat screening is permitted. Acceptable laboratory values are presented in Appendix B.15

• Student or employee under the direct supervision of any of the study investigators

• Any known immunodeficiencies, including complement deficiency, antibody deficiency,chronic granulomatous disease or HIV infection

• A history of prior confirmed N. meningitidis infection

• Hemophilia or other bleeding diatheses.

• Autoimmune disorders; mild autoimmune disorders, such as eczema, are notexclusionary and will be determined by the study physician.

• Unstable psychiatric condition (defined as receiving either <3 months of the samemedication (and dose) or a decompensating event during the previous 3 months) orpsychiatric condition that, in the opinion of the investigator, will compromise theparticipant's ability to comply with protocol requirements

• Known anatomic abnormality of the urethra or urethral meatus (granular hypospadiasis not exclusionary if the study physician believes that the urethral location willnot interfere with inoculation catheter insertion)

• Any immunization in 28 days prior to enrollment

• Self-reported treatment for cancer within the past year

• Receipt of anticoagulants (aspirin or nonsteroidal anti-inflammatory drugs (NSAIDS)are acceptable) within 14 days prior to study entry.

• Use of any systemic immunomodulatory treatment, systemic corticosteroids, (inhaledand topical corticosteroids acceptable), investigational products, interleukins,interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 daysprior to study entry.

• Have donated blood or blood products within 28 days before study vaccination, planto donate blood at any time during the study and up to 28 days after the last blooddraw.

• Allergy to penicillin, cephalosporins or ciprofloxacin or to lidocaine or anycomponent of 4C-MenB vaccine or control vaccines (flu, Influenza vaccine (FLULAVALTM) and Td, TDVAXTM), including latex (confirmed delayed contacthypersensitivity to latex is not exclusionary)

• Treatment with medications that are contraindicated with cefixime, ceftriaxone orciprofloxacin and that cannot be withheld for the single doses given in this study

• Serum creatinine level > 1.1X upper limit of normal (ULN) and deemed clinicallysignificant by the study physician

• Serum ALT level > 1.25X ULN and deemed clinically significant by the study physician

• WBC count < 2.5 or > 15.0 x109/L and deemed clinically significant by the studyphysician

• Absolute neutrophil count (ANC) < 1.0 x 109/L and deemed clinically significant bythe study physician

• Hemoglobin level < 11.0 g/dL or above ULN and deemed clinically significant by thestudy physician

• Urinalysis: Qualitative protein level ≥ 1+ or Red blood cell (RBC) count≥ 6/hpf

• Any condition in the opinion of the investigator that would interfere with theproper conduct of the trial.

Medications not permitted with cefixime or ceftriaxone:

Warfarin Probenecid Aspirin Diuretics such as furosemide Aminoglycoside antibiotics Chloramphenicol

Medications not permitted with ciprofloxacin:

Tizanidine Theophylline Warfarin Glyburide Cyclosporine Probenecid Phenytoin Methotrexate Antacids, multivitamins, and other dietary supplements containing magnesium, calcium, aluminum, iron or zinc Caffeine-containing medications Sucralfate or didanosine chewable or buffered tablets