A Phase 4, Randomised Vaccination Study in Healthy Adults to Investigate the Effects of Acellular Pertussis Vaccine on Colonisation with Bordetella Pertussis Using Controlled Human Infection

Inclusion Criteria:

• Participant (male/female) is born before 1-9-2004 and < 50 years old on the day ofscreening

• Participant has received all primary pertussis vaccines during childhood

• Participant is in good health as confirmed by review of medical history and physicalexamination

• Participant has adequate understanding of the procedures of the study and agrees toabide strictly thereby

• Participant is able to answer all questions of the pre-consent questionnairecorrectly

• Participant is fully conversant in the Dutch language

• Participant is capable and willing to give personal signed informed consent.

• Participant is able to communicate by both mobile telephone and text messaging

• Participant is willing and available to attend all study visits

• Participant agrees to inform his/her general practitioner (GP) about participationin the study

• Participant agrees to provide access to information regarding their vaccinationbackground

• Participant agrees to provide a treating physician access to all study-relatedinformation and data

• Participant is able to arrive within 1h at the Radboudumc from his/her home address.The participant must have a home address and live in the Netherlands

• Participant is able to arrive within 3h at the Radboudumc at any time between Bpinoculation until the day 28 post challenge visit

• Participant is willing to take an antibiotic regimen after inoculation with Bpaccording to the study protocol

• Participant is willing to use infection control measures during social contactduring the study

• Participant is willing to attend to the Radboudumc immediately if they becomesymptomatic

Exclusion Criteria:

• Incapacitated subjects without decision-making capacity.

• A confirmed diagnosis of pertussis in the last two years and/or serum IgG anti-FHA >56 IU/mL

• History of severe adverse reaction associated with a vaccine and/or severe allergicreaction (e.g., anaphylaxis) to any component of the study intervention.

• Bleeding diathesis or condition associated with prolonged bleeding that would, inthe opinion of the investigator, contraindicate intramuscular injection

• Other medical or psychiatric condition including recent (within the past year) oractive suicidal ideation/behavior or laboratory abnormality that may increase therisk of study participation or, in the investigator's judgment, make the participantinappropriate for the study.

• Individuals who are at risk of complications of a prolonged cough, such asindividuals with stress urine incontinence, pelvic floor dysfunction or an inguinalhernia

• Chronic use of i) immunosuppressive drugs (e.g. systemic steroids, steroid nasalspray or isotretinoin), ii) antibiotics, iii) or other immune modifying drugs withinthree months prior to study onset (topical corticosteroids and oral anti-histaminesexempted) or expected use of such during the study period.

• Individuals with a history of autoimmune disease or an active autoimmune diseaserequiring therapeutic intervention.

• Drug or alcohol abuse interfering with normal social function in the period of oneyear prior to study onset

• Diabetes mellitus

• Smoking: Any smoking event in the last month, including (e-)cigarette, joint, cigarand pipe

• Infection with Bp or any other Bordetella species at the baseline for challengevisit

• Individuals who have a history of receiving pertussis vaccination in the last 5years

• Acute illness within 3 days prior to Bp inoculation (including mild upperrespiratory tract infection, common cold, running nose)

• Any antibiotic treatment within 4 weeks before inoculation

• Receipt of any non-study vaccine within 14 days, before and after receiving thestudy vaccine or Bp inoculation

• For female participants: pregnancy, lactation or intention to become pregnant duringthe study. Female volunteers are required to use an effective form of contraceptionduring this study. Acceptable forms of contraception include:

• Established use of oral, injected or implanted hormonal methods ofcontraception

• Placement of an intrauterine device or intrauterine system

• Total hysterectomy

• Barrier methods of contraception (condom or occlusive cap with spermicide)

• Male sterilisation if the vasectomised partner is the sole partner for theparticipant

• True abstinence when this is in line with the preferred and usual lifestyle ofthe participant

• Known hypersensitivity to or contra-indications (including co-medication) for use ofazithromycin or macrolides, see: azitromycine (oraal) (farmacotherapeutischkompas.nl). This includes: Clinically relevant bradycardia,hypokalemia, hypocalcemia and hypomagnesemia, cardiac arrhythmia or severe heartfailure, congenital or acquired QT-prolongation, use of comedication which can causeQT-prolongation or is contraindicated co-medication: for a full list see:azitromycine (oraal) (farmacotherapeutischkompas.nl) - interactions.

• Participation in any other clinical study (unless observational) in the three monthsprior to the start of the study or during the study period

• Being an employee or student of the department of Laboratory Medicine, Radboudumc

• Any other condition or situation that would, in the opinion of the investigator,place the participant at an unacceptable risk of injury or render the participantunable to meet the requirements of the protocol

• Individuals who have inviolable commitments within the study period during thechallenge (28 days in total) to make contact with:

• infants aged < 1 year

• unimmunized children aged < 4 years

• pregnant women >32 weeks who have not received pertussis vaccination at least aweek prior to contact

• chronically ill patients (e.g. asthma, COPD, heart diseases)

• Individuals who have household contacts working with

• infants aged < 1 year

• pregnant women

• The use of mouthwash during the challenge (35 days)