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

Inclusion Criteria:

1. Written signed informed consent form (ICF) obtained before any study-relatedactivities.

2. Participants aged between, and including, 18 and 40 years of age at the time ofsigning the ICF which equals with the time of the first study intervention.

3. Participants who are considered to be in good general health as determined by theinvestigator by medical evaluation including medical history andphysical examinationat enrollment.

4. Participants with a BMI within the range 18.5 to 35 kg/m2 inclusive at screening.

5. POCBP (18-40 years of age) who are not pregnant or breastfeeding or planning tobecome pregnant during the clinical study.

6. 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.

7. POCBP must have a negative urine pregnancy test at each vaccination visit (Visit 1and Visit 5) Refer to Section 8.6.5 for Pregnancy Testing.

8. Participants who are willing and able to comply with the study procedures and arecapable to comply with the requirements of the protocol (e.g. return for follow-upvisits) as determined by the investigator.

Exclusion Criteria:

1. Current or previous, confirmed or suspected disease caused by N. meningitidis and N.gonnorrhoea.

2. Household contact with and/or intimate exposure (e.g. sexual or saliva contact) toan individual with laboratory confirmed N. meningitidis infection during life.

3. Transgender persons in a diagnostic phase (no hormonal intervention) or undergoingtreatment based on the suppression of endogenic hormones (e.g. gonadotropinreleasing hormone analogues).

4. Current or previous infection with hepatitis B, hepatitis C or humanimmunodeficiency virus (HIV) as determined by anamnesis and medical history.

5. Past or current history of immune-mediated and/or autoimmune diseases, as indicatedby the investigator, including but not limited to blood, endocrine, hepatic,muscular, nervous system or skin autoimmune disorders, lupus erythematosus andassociated conditions or disorders (e.g. rheumatoid arthritis, scleroderma) orimmunodeficiency syndromes (including, but not limited to: acquired immunodeficiencysyndromes and primary immunodeficiency syndromes).

6. History of confirmed hypersensitivity, anaphylaxis and/or other severe allergicreactions (e.g., generalized urticaria, angioedema, bronchospasm) to any componentof the study vaccine or excipients (sodium chloride, histidine, sucrose, kanamycinand water for injection), medical products, or medical equipment whose use isforeseen in this study, as determined by the investigator.

7. Clinical conditions representing a contraindication for IM administration and blooddraws, as judged by the investigator, e.g. thrombocytopenia or history of bleedingdisorder (e.g. factor deficiency, coagulopathy, or platelet disorder requiringspecial precautions) or significant bruising or bleeding difficulties.

8. Current history of uncontrolled medical illness (unstable for the past 3 months) asindicated by investigator, e.g. hypertension, diabetes mellitus type 2.

9. Past or current history of any neurological disorder (including but not limited to:demyelinating disorder, encephalitis or myelitis of any origin, congenitalneurological conditions, encephalopathies), Guillain-Barré syndrome and seizuredisorders other than: 1) childhood febrile seizures, or 2) seizures that have notrequired treatment within the last 3 years.

10. History of asplenia, functional asplenia or any condition resulting in the absenceor removal of the spleen.

11. Active malignancy or malignancy within the past 5 years (except basocellularcarcinoma (single lesions) that has been fully removed).

12. History of idiopathic urticaria within the past year.

13. Currently pregnant, breast-feeding or planning to become pregnant. Individuals withpermanent infertility due to an alternate medical cause (e.g. documented bilateraloophorectomy, androgen insensitivity, gonadal dysgenesis) are excluded toparticipate.

14. Any other clinical condition that, in the opinion of the investigator, couldcompromise the participant's safety and/or compliance with the study protocol (e.g.current or recent (< 2 years ago) heavy smoking (> 20 cigarettes per day) or vaping (> 2 mL e-liquid daily, correspond with 20 cigarettes)41 , drug- or alcohol (> 15units for cisgender men and transgender women or > 10 units or cisgender women andtransgender men per week) abuse/addiction.

15. Behavioral or cognitive impairment, unstable psychiatric conditions (e.g. forcedadmission, suicidal thoughts in the last two year) or other psychiatric diseasethat, in the opinion of the investigator, may interfere with study compliance, aswell as with the subject's ability and/or safety to participate in the study. Stablepsychiatric conditions (e.g. under-controlled depression) will be evaluated based onthe investigators judgement.

16. Donation of blood or blood products within 90 days prior to the first vaccinationvisit (Visit 1) until Day 56 (Visit 9).

17. Current or history of anemia and menorrhagia as determined by anamnesis and medicalhistory.

18. Previous vaccination against any group B meningococcal vaccine (Bexsero®, Trumenba®)at any time prior to informed consent.

19. Prior receipt of a live-attenuated vaccine in the 28 days prior to administration ofthe 4CMenB vaccine, within 14 days for subunit or inactivated vaccines or planningto receive a vaccine in between the first and second vaccine administration, as wellas 28 days following administration of the second 4CMenB vaccine dose.

20. Currently participating in another clinical study, or planning to participate inanother study during the study period, or administration of any investigational drugor medical device in the 28 days prior to study vaccination.

21. Prior receipt of blood, blood-derived products or immunoglobulins in the 6 monthsprior to administration of the study vaccine, or planning to receive such productduring the study period.

22. Chronic administration (defined as 14 consecutive days in total) ofimmunosuppressants (e.g. corticosteroids (PO/IV/IM) or other immune-modifying drugs (e.g. antineoplastic agents, radiotherapy) during the period starting 90 days priorto vaccination or planned administration during the study (excluding topical,inhaled and intranasal preparations and intra-articular injections). Forcorticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent.

23. POCBP (cisgender women and transgender men) who use the following contraceptivemethods will not be included in the study

• Oral, injectable, intravaginal (i.e. intravaginal ring) or transdermal combined (oestrogen- and progesterone-containing) hormonal contraception associated withinhibition of ovulation.

• Oral, injectable or implantable progestogen-only hormonal contraceptionassociated with inhibition of ovulation.

24. Current anti-tuberculosis prophylaxis or therapy.

25. Participants with a history of any medical conditions that, in the opinion of theinvestigator, might interfere with the results of the study or pose additional riskto the participants when participating in the study.