Mucosal Immunity Against Neisseria Gonorrhoeae After 4CMenB Vaccination

This is a Phase 2 mechanistic clinical trial to assess the systemic and mucosal immunogenicity of the multicomponent meningococcal serogroup B vaccine (4CMenB or Bexsero (R)) (group 1, 40 subjects) against Neisseria gonorrhoeae, using a placebo vaccine (normal saline) as a comparator (group 2, 10 subjects). There will be approximately 50 participants, ages 18-49, both male and non-pregnant female subjects, enrolled at 1 site in the US. The goal will be to ensure adequate representation of subjects by sex in both treatment groups. The enrollment will be stratified by both sex and treatment arm. A subset of subjects in each treatment group (N=16 in Group 1, N=4 in Group 2) will undergo rectal mucosal biopsy at two time points (baseline and following the second vaccination) for assessment of tissue Neisseria gonorrhoeae (GC) specific cellular responses. During enrollment of the "biopsy cohort" male and non-pregnant female subjects will be randomized 4:1 to either 4CMenB or placebo, up to a maximum of 10 male and 10 non-pregnant female subjects. All subjects will undergo sampling of mucosal secretions for testing for antibodies against Neisseria gonorrhoeae (GC). Male subjects will undergo oropharyngeal and rectal mucosal sampling, and female subjects will undergo oropharyngeal, vaginal and rectal mucosal sampling. Group 1 (approximate N=40) will receive two doses of 4CMenB on Day 1 and Day 29. Group 2 (approximate N=10) will receive two placebo injections on Day 1 and Day 29. Both groups will receive a single-dose prefilled syringe that is administered intramuscularly (0.5-mililter each). The duration of each subject's participation is approximately 8 months, from recruitment through the last study visit, and the length of the study is estimated for 14 months. The primary objective is to characterize the rectal mucosal Immunoglobulin G (IgG) antibody response to Neisseria gonorrhoeae (GC) elicited by the 4CMenB vaccine as compared with the placebo vaccine (normal saline) in healthy adult subjects. The secondary objectives are: 1) To characterize the serum IgG antibody response to Neisseria gonorrhoeae (GC) elicited by the 4CMenB vaccine as compared with the placebo vaccine in healthy adult subjects, 2) To assess the safety and reactogenicity of 4CMenB in healthy adult subjects.

Inclusion criteria

• Must be aged 18-49 years old (inclusive) at the time of vaccination.
• Must be able to provide written informed consent.
• Must have a body mass index (BMI) >/= 18.5 and < 35.0 kg/m2
• Must be in good health based on physical examination, vital signs*, medical history, safety labs** (as applicable to the rectal biopsy and no biopsy cohorts) and the investigator's clinical judgment.

*Vital signs must be within the normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and the blood pressure may be retaken.

**Safety labs must be within the normal ranges and the normal ranges will be those used by the reference clinical lab.

• For female subjects only: If a female participant is of childbearing potential*, she must use contraception** from 30 days before study product administration through the end of study participation.

*A woman is considered of childbearing potential unless post-menopausal (defined as history of >/= 1 year of spontaneous amenorrhea), or permanently surgically sterilized (bilateral oophorectomy, salpingectomy, hysterectomy).

**Acceptable methods of contraception include: abstinence or no sex with a male, monogamous relationship with a man who had a vasectomy at least 6 months before the 1st study vaccine, prescription oral contraceptives, intrauterine device (IUD), birth control implants or injections, contraceptive patch, vaginal ring, condoms and diaphragms/cervical cap with spermicide ("double barrier" method).

• Must be available and willing to participate for the duration of this trial.
• Willing to provide mucosal samples: vaginal secretions for women and oropharyngeal and rectal secretions for men and women.
• For the rectal biopsy cohort only, willing to provide rectal biopsies.

Exclusion criteria

• Has ever been diagnosed with meningococcal infection or gonococcal infection at any anatomic site.
• Has ever received any serogroup B meningococcal vaccine.
• Any positive test result for STI (including Neisseria gonorrhoeae (GC) Chlamydia trachomatis (CT), Rapid Plasma Reagin (RPR) and Human Immunodeficiency Virus (HIV)) at screening*.

*Female subjects will also be tested for Trichomonas at screening.

• Any history of Chlamydia trachomatis or syphilis infection at any body site in the preceding 12 months
• Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products.
• Has severe allergy or anaphylaxis to latex.
• Has an acute illness or temperature >/= 38.0 degrees Celsius on Day 1*.

*Subjects with fever or acute illness on the day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days.

• Has a history of a bleeding disorder, or is taking chronic anti-coagulant (e.g. warfarin, direct thrombin inhibitors, heparin products, etc.), anti-platelet, or non-steroidal anti-inflammatory drugs (NSAID) therapy.
• Has history of autoimmune disease, or clinically significant cardiac, pulmonary, gastrointestinal, hepatic, rheumatologic, or renal disease by history or physical examination.
• Has history of active malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure*.

*Subjects with a history of skin cancer must not be vaccinated at the previous tumor site.

• Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy*.

*Anti-cancer chemotherapy or radiation therapy within the preceding 3 years, or long-term (>/= 2 weeks within the previous 3 months) systemic corticosteroid therapy (at a dosage of >/= 0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) are allowed.

• Is post-organ and/or stem cell transplant, whether or not on chronic immunosuppressive therapy.
• Had major surgery (per the investigator's judgment) within 4 weeks before study entry or planned major surgery during this trial.
• Has history of diabetes* mellitus type 1 or type 2, including cases controlled with diet alone*.

*History of isolated gestational diabetes is not an exclusion criterion.

• Received live attenuated vaccines from 30 days before first vaccination until 30 days after second vaccination.
• Received killed or inactivated vaccines* from 14 days before first vaccination until 14 days after second vaccination.

*For inactivated influenza vaccine, from 7 days before either vaccination until 7 days after either vaccination.

• Received mRNA, viral vector, or any other technology platform Corona Virus Disease-19 (COVID-19) vaccine within 14 days prior to first dose of the study product.*

*COVID-19 vaccination should take priority over administration of the study product.

• Received experimental therapeutic agents within 12 months before first vaccination or plans to receive any experimental therapeutic agents during this trial except for Emergency Use Authorization (EUA) COVID-19 therapy.*

*Only exclusionary if, in the opinion of the investigator, they would interfere with safety or endpoint assessment.

• Is currently participating or plans to participate in another clinical study which would involve receipt of an investigational product or undergoing a procedure*.

*Only exclusionary if, in the opinion of the investigator, they would interfere with safety or endpoint assessment.

• Received blood products or immunoglobulin in the 3 months before study entry or planned use during this trial.
• Has major psychiatric illness in the past 12 months that in the opinion of the investigator would preclude participation.
• Has current alcohol use or current or past abuse of recreational or narcotic drugs by history as judged by the investigator to potentially interfere with study adherence.
• In the opinion of the investigator cannot communicate reliably, is unlikely to adhere to the requirements of this trial, or has any condition which would limit the ability to complete this trial.
• Is pregnant or breast feeding.