4C-MenB Vaccine for Gonorrhea

Overseen By Arlene Sena-Soberano, MD, MPH

Age: 18 - 65

Sex: Male

Trial Phase: Phase 2

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Warfarin, Probenecid, Theophylline, others

Disqualifiers: Immunodeficiencies, Autoimmune disorders, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a vaccine typically used for meningitis (a serious infection of the brain and spinal cord) can also protect against gonorrhea, a common sexually transmitted infection. Participants will receive different vaccines, including the meningitis vaccine 4C-MenB (also known as Bexsero), to evaluate their effectiveness in preventing gonorrhea. Men living in central North Carolina, who are generally healthy and have never received this specific meningitis vaccine, might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but certain medications are not allowed with the antibiotics used in the study. You should avoid medications like warfarin, probenecid, and some others listed in the trial details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the 4C-MenB vaccine, also known as Bexsero™, is generally safe. The FDA has approved this vaccine to prevent infections caused by Neisseria meningitidis, a bacterium similar to the one that causes gonorrhea.

Studies have found that most people tolerate the vaccine well. Common side effects include mild reactions such as pain at the injection site, fatigue, and headaches. These side effects are usually temporary and resolve on their own. No serious side effects have been directly linked to the vaccine in these studies.

Overall, the current use of 4C-MenB to prevent meningitis supports its safety, making it a promising option for preventing gonorrhea as well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for gonorrhea involve antibiotics that target the bacteria directly. However, the 4C-MenB vaccine, currently being studied, works differently by stimulating the body's immune system to recognize and fight the bacteria before it causes an infection. Researchers are excited about this approach because it could potentially provide long-lasting protection and reduce reliance on antibiotics, which is crucial as antibiotic resistance continues to rise. This vaccine leverages BEXSERO™, originally designed for meningitis B, showing promise in offering cross-protection against gonorrhea.

What evidence suggests that the 4C-MenB vaccine could be effective for gonorrhea?

Research shows that the 4C-MenB vaccine, also known as Bexsero™, may help protect against gonorrhea. Studies have found that receiving at least one dose of this vaccine can lower the risk of gonorrhea infection by 23% to 47%. Another analysis suggested the vaccine is about 32% to 41% effective. This effectiveness arises because the bacteria causing meningitis and gonorrhea are very similar, and the vaccine targets them. Observational studies also suggest that the protection can last for up to three years. In this trial, participants in the experimental arm will receive the recommended two doses of Bexsero™ before the bacterial challenge, while those in the control arm will receive control vaccines before the challenge and Bexsero™ afterward. Overall, the vaccine seems promising in reducing gonorrhea infections. ^{5 6 7 8 9}

Who Is on the Research Team?

Joseph A Duncan, MD, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for healthy males aged 18-35 in central North Carolina who haven't been vaccinated against Neisseria meningitidis group B. Participants must consent to avoid sexual activity during certain phases, not have a history of severe reactions to antibiotics or vaccines, and be able to attend all study visits.

Inclusion Criteria

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

Denies current drug abuse that would interfere with study activities

I do not have a history of unusual bleeding.

Exclusion Criteria

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

Have donated blood or blood products within 28 days before study vaccination, plan to donate blood at any time during the study and up to 28 days after the last blood draw

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Vaccination

Participants receive two doses of vaccines (either BEXSERO™ or control vaccines) prior to the bacterial challenge phase

4 weeks

2 visits (in-person)

Neisseria gonorrhoeae Challenge

Participants receive a suspension containing N. gonorrhoeae and are monitored for development of urethritis

1-10 days

Daily visits (in-person)

Post-Challenge Vaccination

Participants receive two doses of vaccines not received prior to the challenge (either BEXSERO™ or control vaccines)

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 4C-MenB

Trial Overview The trial tests if the FDA-approved Bexsero™ vaccine for meningitis B also prevents gonorrhea infection. It's a double-blind study where participants receive either the meningitis vaccine or other vaccines (flu and tetanus/diptheria), followed by an experimental challenge with gonorrhea bacteria.

How Is the Trial Designed?

Group I: Experimental arm Experimental Treatment 7 Interventions

All participants receive two immunizations prior to the bacterial challenge phase and two immunizations after the challenge phase. Individuals assigned to the experimental arm receive the recommended two doses of BEXSERO™ prior to bacterial challenge and control vaccines (FLULAVAL™ and TDVAX™) in the post-challenge vaccination phase. For bacterial challenge, all participants receive a suspension containing 10\^6 colony-forming units of N. gonorrhoeae strain FA1090 delivered to the anterior urethra. Participants receive 100% effective antibiotic treatment for N. gonorrhoeae strain FA1090 infection when (1) requested by the participant regardless of signs, symptoms or positive cultures, (2) urethral discharge is observed by the examining clinician or reported by the participant, or (3) 10 days afterurethral inoculation with bacterial product, regardless of infection status.

Group II: Control arm Experimental Treatment 7 Interventions

All participants receive two immunizations prior to the bacterial challenge phase and two immunizations after the challenge phase. Individuals assigned to the control arm receive control vaccines that have no relevance to N. gonorrhoeae infection (FLULAVAL™ and TDVAX™) prior to bacterial challenge and then receive two doses of BEXSERO™ in the post-challenge vaccination phase. For bacterial challenge, all participants receive a suspension containing 10\^6 colony-forming units of N. gonorrhoeae strain FA1090 delivered to the anterior urethra. Participants receive 100% effective antibiotic treatment for N. gonorrhoeae strain FA1090 infection when (1) requested by the participant regardless of signs, symptoms or positive cultures, (2) urethral discharge is observed by the examining clinician or reported by the participant, or (3) 10 days afterurethral inoculation with bacterial product, regardless of infection status.

4C-MenB is already approved in European Union, United States for the following indications:

Approved in European Union as Bexsero for:

• Invasive meningococcal disease caused by serogroup B

Approved in United States as Bexsero for:

• Invasive meningococcal disease caused by serogroup B in adolescents and young adults aged 10 through 25 years

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

The introduction of the Bexsero® meningococcal B vaccine into Spain's routine vaccination schedule could prevent 54% of invasive meningococcal disease cases and deaths with a 3+1 dosage, but it is currently not cost-effective at the existing price, with an incremental cost-utility ratio (ICUR) of 351,389 €/QALY.

For the vaccine to be considered cost-effective, the price would need to be reduced to 1.45 € for the 3+1 dosage or 3.37 € for the 2+1 dosage, indicating that pricing plays a crucial role in vaccine policy decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Economic evaluation of the introduction of 4CMenB (Bexsero®) in the national vaccine schedule in Spain]. Ruiz-Montero, R., Epstein, D., Guzmán Herrador, B., et al.[2021]

The multicomponent meningococcal serogroup B vaccine (4CMenB) effectively generates protective antibody responses in infants, adolescents, and adults, with the majority of participants achieving seroprotective levels after the recommended doses in clinical trials.

While the vaccine is generally well-tolerated, infants experienced more systemic side effects, such as fever, when 4CMenB was given alongside routine vaccinations, indicating a need for monitoring during coadministration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicomponent meningococcal serogroup B vaccine (4CMenB; Bexsero(®)): a review of its use in primary and booster vaccination. Carter, NJ.[2016]

A review of 1,867 adverse event reports following the administration of the MenB-4C vaccine showed that 96% of these reports were classified as non-serious, indicating a favorable safety profile for the vaccine.

The most common adverse events reported were injection site pain, fever, and headache, which align with the expected safety outcomes from clinical studies, suggesting no new safety concerns have emerged since the vaccine's approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety surveillance of meningococcal group B vaccine (Bexsero®), Vaccine Adverse Event Reporting System, 2015-2018. Perez-Vilar, S., Dores, GM., Marquez, PL., et al.[2023]

The MenB-4C vaccine was administered to 16,974 individuals, with a low incidence of serious adverse events (SAEs), including only one case of anaphylaxis, indicating that the vaccine is generally safe.

Most adverse events reported were mild, such as arm pain and fever, and consistent with previous studies, supporting the vaccine's use during meningococcal outbreaks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of a meningococcal group B vaccine used in response to two university outbreaks. Duffy, J., Johnsen, P., Ferris, M., et al.[2022]

The MenB-4C vaccine was found to be protective against gonorrhoea, with a complete vaccination series showing a 40% effectiveness and a partial series showing 26% effectiveness in individuals aged 16-23 years in two US cities.

Among 167,706 infections analyzed, complete vaccination significantly reduced the prevalence of gonorrhoea compared to no vaccination, suggesting that this vaccine could provide cross-protection against Neisseria gonorrhoeae and highlights the potential for developing effective gonococcal vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of a serogroup B outer membrane vesicle meningococcal vaccine against gonorrhoea: a retrospective observational study. Abara, WE., Bernstein, KT., Lewis, FMT., et al.[2023]

In a study of 1051 men living with HIV, those who received two doses of the 4CMenB vaccine had a 44% lower risk of contracting gonorrhea compared to those who did not receive the vaccine, indicating its effectiveness in this population.

The study, which followed participants for an average of 3.8 years, suggests that the 4CMenB vaccine may provide significant protection against gonorrhea among men who have sex with men and have a history of sexually transmitted infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meningococcus B Vaccination Effectiveness Against Neisseria gonorrhoeae Infection in People Living With HIV: A Case-Control Study. Raccagni, AR., Galli, L., Spagnuolo, V., et al.[2023]

The MenB-4C vaccine (Bexsero®) effectively induces serum bactericidal antibodies (SBA) against Neisserial Heparin binding antigen (NHba), with depletion of anti-NHba antibodies resulting in a significant decrease in SBA titers by 43-79%, indicating its important role in vaccine efficacy.

While anti-NHba antibodies contribute to SBA, some strains expressing high levels of NHba may still evade the immune response, highlighting the need for further understanding of the vaccine's limitations against certain bacterial strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C. Partridge, E., Lujan, E., Giuntini, S., et al.[2018]

The protein-based meningococcal group B vaccine Bexsero(®) may provide some protection against secondary infections, but its early effectiveness after a single dose is low, especially in young children who are at higher risk.

The estimated number needed to vaccinate (NNV) to prevent one secondary case is over 1000 in household settings, indicating that while Bexsero(®) could be useful in outbreaks, its practical application for individual cases may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing secondary cases of invasive meningococcal capsular group B (MenB) disease using a recently-licensed, multi-component, protein-based vaccine (Bexsero(®)). Ladhani, SN., Cordery, R., Mandal, S., et al.[2022]

The Meningococcal Antigen Typing System (MATS) accurately predicts the strain coverage of the 4CMenB vaccine, showing a significant association with serum bactericidal antibody assay results from a representative sample of MenB strains in England and Wales.

MATS predicted a 70% strain coverage, which was confirmed by an 88% killing rate in the hSBA assay, demonstrating that MATS is a reliable tool for assessing the vaccine's effectiveness in infants and adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. Frosi, G., Biolchi, A., Lo Sapio, M., et al.[2019]

Vaccination of men who have sex with men (MSM) against gonorrhoea using the 4CMenB vaccine, particularly through a risk-based approach, is likely to be cost-effective and could avert a significant number of cases while saving healthcare costs over a 10-year period.

The study suggests that improving the efficacy of a gonorrhoea vaccine is more valuable than extending its duration of protection, highlighting the importance of focusing on vaccine effectiveness in future development efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public health impact and cost-effectiveness of gonorrhoea vaccination: an integrated transmission-dynamic health-economic modelling analysis. Whittles, LK., Didelot, X., White, PJ.[2022]

The 4CMenB vaccine, primarily designed to protect against meningococcal infections, may also provide some level of protection against Neisseria gonorrhoeae, the bacteria responsible for gonorrhea, although more research is needed to confirm this.

Understanding the immune response to gonococcal infections is complex, as the mechanisms of protection against local infections (like gonorrhea) may differ from those against systemic infections (like meningitis), highlighting the need for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insight into Prevention of Neisseria Gonorrhoeae: A Short Review. La Fauci, V., Lo Giudice, D., Squeri, R., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11782638/

Effectiveness of menb-4C vaccine against gonorrhea Results: Eight papers met our eligibility criteria. Receipt of ≥1 dose of MenB-4C vaccine was 23%–47% effective against gonorrhea. Two ...

2. academic.oup.com academic.oup.com/jid/article/231/1/61/7724768

Effectiveness of MenB-4C Vaccine Against Gonorrhea Pooled vaccine effectiveness against gonorrhea after receipt of ≥1 MenB-4C dose was 32.4%. The high sequence identity (80%–90%) between the outer membrane ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X25004852

Meningococcal vaccines show effectiveness in gonorrhoea ... The pooled analysis yielded a vaccine effectiveness (VE) of 38 % [95 % CI:22 %–50 %; I2 = 55 %]. Including only the 4CMenB vaccine, VE was 41 % ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04415424?cond=gonorrhea&term=bexsero&rank=1

NCT04415424 | Efficacy Study of 4CMenB (Bexsero®) to ... To measure whether the 4CMenB vaccine , when administered in a 2-dose regimen at 0 and 3 months, changes the incidence of the first episode of N. gonorrhoeae.

5. canada.ca canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2025-51/issue-8-august-2025/effectiveness-four-component-protein-based-meningococcal-vaccine-against-neisseria-gonorrhoeae.html

Effectiveness of the four-component protein-based ... Results: Observational studies have shown protection against gonorrhea infection ranging from 35% to 59% for up to three years after the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04350138

NCT04350138 | Safety and Efficacy Study of ... gonorrhoeae infection. Approximately 2,200 participants are expected to be ... Gonorrhea(https://medlineplus.gov/gonorrhea.html). FDA Drug and Device ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6743822/

The Serogroup B Meningococcal Vaccine Bexsero Elicits ... Neisseria gonorrhoeae and Neisseria meningitidis are closely-related bacteria that cause a significant global burden of disease. Control of gonorrhoea is ...

8. academic.oup.com academic.oup.com/ofid/article/11/11/ofae562/7863731

Breakthrough Rectal Neisseria gonorrhoeae Infections After ... 4CMenB appears to be effective in reducing Neisseria gonorrhoeae (Ng) infections. Aims are to assess factors associated with breakthrough rectal Ng after 4 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10062254/

An open-label randomised controlled trial evaluating the ... ... 4CMenB as a general population gonorrhoea prevention strategy. ... The serogroup B meningococcal vaccine Bexsero elicits antibodies to Neisseria gonorrhoeae.