"Healthy volunteers" In this project we will establish whether naturally induced mucosal CD25+ T regulatory activity in adults and adolescents modulates the mucosal immune response to systemic MenB OMV vaccination
Conditions
Interventions
Product Name: meningococcal serogroup B outer membrane vesicl
Product Code: MeNZB
Pharmaceutical Form: Suspension for injection
Sponsors
University Hospitals Bristol NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •written informed consent and agreement for samples to be sent overseas •adults and adolescents 16-40 years scheduled to undergo routine tonsillectomy •in good health at the time of entry into the study as determined by medical history, physical examination and clinical judgment of the investigator •availability for all the visits scheduled in the study .At least eight weeks prior to the expected date of tonsillectomy. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •tonsillectomy for allergic conditions •receipt of or intent to immunize with any vaccination (other than influenza vaccine or post-exposure tetanus vaccination) or investigational agents within 50 days prior to enrolment and throughout the study period •previous receipt of any MenB vaccine •chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs (Inhaled and topical steroids will not be allowed.) •history of confirmed or suspected meningococcal infection or close contact with an individual with culture or PCR proven N. meningitidis serogroup B within the previous 60 days •pregnancy (or plans to become pregnant during study)* or breast feeding •not taking or unwilling to take sufficient measures to avoid pregnancy occurring for the duration of the study period** •any chronic or progressive disease (eg neoplasm, cardiac, respiratory, liver, gastrointestinal, renal, neurological disease, autoimmune disease, blood dyscrasias or diathesis) or history of dependence/abuse of drugs or alcohol •any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection •administration of immunoglobulins and/or any blood products in the last year or planned administration during the study period •history of any anaphylactic shock, asthma, urticaria or any other allergic reaction after previous vaccinations, or known hypersensitivity to any vaccine component •fever (axillary/tympani temperature >= 38.5°C) within the past 24 hours or significant acute or chronic infection within the previous 7 days •significant acute or chronic infections requiring systemic antibiotic treatment within the past 14 days •not available for all the visits scheduled during the study period •any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives •participation in another clinical trial within last 90 days or planned for during the study * A pregnancy test (urine) on the scheduled day of each vaccination will be required for any female wishing to participate in the study as well as giving basic menstrual cycle information to cover the period in which and individual may be pregnant but this would not be ascertained by the chemical test. ** Females of childbearing age who have not used or do not plan to use acceptable birth control measures for the duration of the study. Oral, injected or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device are considered acceptable forms of birth control. If sexually active the subject should have been using one of the accepted birth control methods at least two months prior to study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We ask whether specialised immune cells called CD25+ regulatory T cells (Treg)operating in the back of the throat explain the failure of immunisation to boost mucosal T-cell immunity in teenagers and young adults.;Secondary Objective: 1) Determine whether it is immunity to particular MenB molecules (antigen specificity of the mucosal CD25+ Treg population) that regulates MenB immunity. 2) Investigate the impact of this regulation on other mucosal immune cells (B cell memory).;Timepoint(s) of evaluation of this end point: Blood samples will be assessed right before the scheduled tonsillectomy and 12 weeks before it, saliva samples will be assessed right before the scheduled tonsillectomy, 12 weeks, and 6 weeks before it.;Primary end point(s): 1. T cell phenotype and function: Mucosal and systemic T-cells (CD45RO+ or CD25+ depleted) will be assessed for proliferation and phenotype. 2. Mucosal B cell antibody production: The number of tonsil cells producing vaccine protein antigen specific IgG, IgA and IgM will be measured both immediately following cell isolation and also following antigenic and mitogenic stimulation in culture. 3. Salivary antibody: anti-meningococcal antibodies (igG and IgA) will be measured by ELISA. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: N/A;Secondary end point(s): N/A | — |
Countries
United Kingdom
Contacts
Public ContactMary Perkins
University Hospital Bristol NHS Foundation Trust
Outcome results
None listed