Investigating Gender and Sex Differences in Immune Responses Through Vaccination of Transgender and Cisgender Persons

NCT06832514 | Recruiting Phase 4

• 2 other identifiers: ONZ-2024-04612024-515599-11-00
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Sexual differences are a well-established source of biological variation in immune system functioning, with men often displaying lower adaptive immune responses (e.g. antibody production) to infections and vaccinations compared to women. The impact of sex and gender on immune responses and immune functioning warrants more in-depth investigation. This study is an investigator-initiated project aimed at prospectively assessing the immune response towards a vaccine in transgender and cisgender individuals. Transgender individuals retain their chromosomal sex while undergoing a significant hormonal shift that aligns with their experienced gender. Immune responses induced by the four-component meningococcal serogroup B (4CMenB; Bexsero®) vaccine will be evaluated in transgender individuals and compared with responses observed in cisgender individuals. Both humoral and cellular immune responses induced by two doses of the 4CMenB vaccine will be quantified and analysed. This approach is expected to provide new insights into the effects of gender and sex differences on innate and adaptive immune responses.

Conditions

Meningococcal Meningitis, Serogroup B; Transgender Persons; Sex Differences in Immune Response; Vaccination

Keywords

Gender

Outcome Measures

Primary Outcomes (1)

• Characterise humoral, adaptive immune responses elicited by two administrations of 4CMenB in transgender and cisgender healthy participants, aged 18 to 50 years.

  The human serum bactericidal antibody titers (hSBA) against reference strains for factor H binding protein (fHbp), Neisseria adhesin A (NadA) and Porine A (PorA) in transgender and cisgender participants.

  From the first vaccination visit to two months post-primary vaccination

Secondary Outcomes (1)

• Characterise the cellular (CD4+ and CD8+ T cell), adaptive immune responses elicited by two administrations of 4CMenB in transgender and cisgender healthy participants, aged 18 to 50 years.

  From the first vaccination visit to two months post-primary vaccination

Other Outcomes (5)

• Characterise innate immune responses elicited by two administrations of 4CMenB in transgender and cisgender healthy participants, aged 18 to 50 years

  From the first vaccination visit to seven days post-secondary vaccination

• Cellular (CD4+ and CD8+ T cell), adaptive immune responses elicited by two administrations of 4CMenB in transgender and cisgender healthy participants, aged 18 to 50 years.

  From 7 days post-primary vaccination to 180 days post-primary vaccination

• Cellular, regulatory T (Treg) cell immune responses elicited by two administrations of 4CMenB in transgender and cisgender healthy participants, aged 18 to 50 years.

  From the first vaccination visit to 180 days post-primary vaccination

Study Arms (4)

4CMenB vaccination cisgender men

EXPERIMENTAL

The four component meningococcal serogroup B (4CMenB) vaccine will be administered to 30 cisgender men via two intramuscular injections, with a one month interval.

Biological: Serogroup B meningococal vaccine

4CMenB vaccination cisgender women

EXPERIMENTAL

The four component meningococcal serogroup B (4CMenB) vaccine will be administered to 30 cisgender women via two intramuscular injections, with a one month interval.

Biological: Serogroup B meningococal vaccine

4CMenB vaccination transgender women

EXPERIMENTAL

The four component meningococcal serogroup B (4CMenB) vaccine will be administered to 30 transgender women via two intramuscular injections, with a one month interval.

Biological: Serogroup B meningococal vaccine

4CMenB vaccination transgender men

EXPERIMENTAL

The four component meningococcal serogroup B (4CMenB) vaccine will be administered to 30 transgender men via two intramuscular injections, with a one month interval.

Biological: Serogroup B meningococal vaccine

Interventions

Serogroup B meningococal vaccine BIOLOGICAL

The 4CMenB vaccine will be administered via two intramuscular (IM) injections in the non-dominant upper arm, with a one month interval.

Also known as: Four component meningococcal serogroup B vaccine, 4CMenB, Bexsero

4CMenB vaccination cisgender men; 4CMenB vaccination cisgender women; 4CMenB vaccination transgender men; 4CMenB vaccination transgender women

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written signed informed consent form (ICF) obtained before any study-related activities.
• Participants aged between, and including, 18 and 50 years of age at the time of signing the ICF which equals with the time of the first study intervention.
• Participants who are considered to be in good general health as determined by the investigator by medical evaluation including medical history andphysical examination at enrollment.
• Participants with a BMI within the range 18.5 to 35 kg/m2 inclusive at screening.
• POCBP (18-50 years of age) who are not pregnant or breastfeeding or planning to become pregnant during the clinical study.
• Transgender persons need to be under stable gender-affirming hormone therapy (GAHT) for at least 6 months. Compliance needs to be documented by hormonal lab tests.
• POCBP must have a negative urine pregnancy test at each vaccination visit (Visit 1 and Visit 5) Refer to Section 8.6.5 for Pregnancy Testing.
• Participants who are willing and able to comply with the study procedures and are capable to comply with the requirements of the protocol (e.g. return for follow-up visits) as determined by the investigator.

You may not qualify if:

• Current or previous, confirmed or suspected disease caused by N. meningitidis and N. gonnorrhoea.
• Household contact with and/or intimate exposure (e.g. sexual or saliva contact) to an individual with laboratory confirmed N. meningitidis infection during life.
• Transgender persons in a diagnostic phase (no hormonal intervention) or undergoing treatment based on the suppression of endogenic hormones (e.g. gonadotropin releasing hormone analogues).
• Current or previous infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV) as determined by anamnesis and medical history.
• Past or current confirmed or suspected immune-suppressive or immune-deficient condition, at the discretion of the investigator, including but not limited to blood, endocrine, hepatic, muscular, nervous system or skin autoimmune disorders, lupus erythematosus and associated conditions or disorders (e.g. rheumatoid arthritis, scleroderma) or immunodeficiency syndromes (including, but not limited to: acquired immunodeficiency syndromes and primary immunodeficiency syndromes).
• History of confirmed hypersensitivity, anaphylaxis and/or other severe allergic reactions (e.g., generalized urticaria, angioedema, bronchospasm) to any component of the study vaccine or excipients (sodium chloride, histidine, sucrose, kanamycin and water for injection), medical products, or medical equipment whose use is foreseen in this study, as determined by the investigator.
• Clinical conditions representing a contraindication for IM administration and blood draws, as judged by the investigator, e.g. thrombocytopenia or history of bleeding disorder (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties.
• History of asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.
• Active malignancy or malignancy within the past 5 years that, in the opinion of the investigator, may affect immune response or participant safety - except for localized and fully treated cancers not requiring long-term therapy such as chemotherapy or radiotherapy (e.g. completely resected basal cell carcinoma, cervical intraepithelial neoplasia, melanoma in situ, early-stage thyroid cancer), based on the investigator's clinical judgement.
• History of idiopathic urticaria within the past year.
• Currently pregnant, breast-feeding or planning to become pregnant. Cisgender women with permanent infertility due to an alternate medical cause (e.g. documented bilateral oophorectomy, androgen insensitivity, gonadal dysgenesis) are excluded to participate. For individuals with permanent infertility due to an alternate medical cause other than the above, investigator discretion should be applied to determining study entry. Additionally, cisgender women in a postmenopausal state, defined as no menses for 12 months without an alternative medical cause are also excluded to participate. Refer to
• Any other clinical condition that, in the opinion of the investigator, could compromise the participant's safety and/or compliance with the study protocol (e.g. current or recent (\< 1 years ago) heavy smoking (\> 20 cigarettes per day) or daily heavy vaping (equivalent to 20 cigarettes), drug- or alcohol (\> 15 units for cisgender men and transgender women or \> 10 units or cisgender women and transgender men per week) abuse/addiction.
• Behavioral or cognitive impairment, unstable psychiatric conditions (e.g. forced admission, suicidal thoughts in the last two year) or other psychiatric disease that, in the opinion of the investigator, may interfere with study compliance, as well as with the subject's ability and/or safety to participate in the study. Stable psychiatric conditions (e.g. under-controlled depression) will be evaluated based on the investigators judgement.
• Donation of blood or blood products within 90 days prior to the first vaccination visit (Visit 1) until Day 56 (Visit 9).
• Previous vaccination against any group B meningococcal vaccine (Bexsero®, Trumenba®) at any time prior to informed consent.

Sponsors & Collaborators

• University Hospital, Ghent: collaborator
• Centre for Vaccinology - CEVAC: collaborator
• University Ghent: lead

Study Sites (1)

CEVAC, University Hospital Ghent, Belgium

Ghent, 9000, Belgium

RECRUITING

MeSH Terms

Conditions

Meningitis, Meningococcal; Coitus

Interventions

4CMenB vaccine

Condition Hierarchy (Ancestors)

Meningitis, Bacterial; Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases; Sexual Behavior; Behavior

Study Officials

• Prof. Dr. Isabel Leroux-Roels, PhD, MD

  CEVAC, University Hospital Ghent, Belgium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof. Dr. Isabel Leroux-Roels, PhD, MD

CONTACT

+3293322068; isabel.lerouxroels@uzgent.be

Dr. Valentino D'Onofrio, PhD

CONTACT

+3293322068; valentino.donofrio@uzgent.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 250 healthy adults will be recruited, with 120 completing the trial, and divided in the following 4 cohorts, each consisting of 30 healthy adult participants aged 18-50 years (inclusive): * Cohort 1: Transgender men (n=30) * Cohort 2: Transgender women (n=30) * Cohort 3: Cisgender men (n=30) * Cohort 4: Cisgender women (n=30) Each particpant will receive the four-component meningococcal serogroup B (4CMenB, Bexsero) vaccine as two intramuscular doses, with a one month interval.

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 18, 2025
• Study Start: January 31, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)