This study aims to investigate gene expression following vaccination with 4CMenB and relate this to vaccine reactions and to immune response
Conditions
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Healthy infants of two Caucasian parents (self-defined by parent) born between 37 and 42 weeks of gestation aged 8-12 weeks at time of first visit •Parent or legal guardian willing and able to comply with the requirements of the protocol and have internet access for the duration of the study. •Parent/legal guardian who have given informed consent for their child’s participation in the study Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: •Non-Caucasian infants •Children of parents who are on the delegation log for this study •Parent/ legal guardian under the age of 18 •History of invasive meningococcal B disease •Previous vaccination with meningococcal serogroup B vaccine •History of being a household contact with a case of confirmed bacterial meningitis •Prior administration of any vaccine or planned administration of any vaccine not specified in the study protocol, with the exception of Hepatitis B vaccine and Influenza vaccines (which can be given 14 days before or after study vaccines), or BCG (which can be administered 28 days before or after study vaccines) •Prior or planned receipt of any other investigational vaccine or drug •Confirmed or suspected immunodeficiency •A family history of congenital or hereditary immunodeficiency, or maternal HIV •Receipt of more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid). Nasal, topical or inhaled steroids are allowed. •History of allergy to any component of the vaccine •Major congenital defects or serious chronic illness •History of any neurologic disorders or seizures •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period •Any other condition which, in the opinion of the investigator, may interfere with the ability to fulfil study requirements (this may include plans to move house and language comprehension). •No internet access for the duration of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Analysis of differentially expressed genes in whole blood at 4hr, 24hr, 3d and 7d timepoints following vaccination with 4CMenB and routine immunisations, or routine immunisations alone.; Secondary Objective: 1. To compare gene expression following vaccination with 4CmenB to immunogenicity as determined by serum bactericidal antibody titres (a measure of how well the body has made antibodies capable of killing MenB)against reference strains of serogroup B N. meningitidis. 2. To investigate changes in the epigenome within individuals following vaccination with 4CMenB. 3. To relate changes in gene expression to changes in B cell populations. 4. To relate changes in gene expression to changes in plasma proteins. 5. To describe any changes in oro-pharyngeal Neiserrial flora occurring after vaccination,as determined by analysis of the pharyngeal microbiome. Exploratory objectives 1. To explore relationships between reactogenicity, gene expression and immunogenicity (are gene expression patterns different between good / poor responders, are fever and immunogenicity related) 2. To explore genetic determinants of response to vaccination with 4CMenB 3. To explore the relati ;Timepoint(s) of evaluation of this end point: Analysis of differentially expressed genes in whole blood at 4hr, 24hr, 3d and 7d time points following the 2nd and 3rd doses of 4CMenB vaccine when given at 2, 4 and 12 months of age together with routine immunisations, or following routine immunisations alone given at equivalent time points;Main Objective: To describe the kinetics of global gene expression (i.e. the pattern of which genes are switched on/off) in whole blood, following vaccination with 4CMenB vaccine in healthy infants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To compare gene expression following vaccination with 4CMenB to immunogenicity as determined by serum bactericidal antibody titres against reference strains of serogroup B N. meningitidis • To investigate changes in the epigenome within individuals following vaccination with 4CMenB • To relate changes in gene expression to changes in B cell populations • To relate changes in gene expression to changes in plasma proteins • To describe any changes in the oro-pharyngeal flora occurring after vaccination, as determined by analysis of the overall oro- pharyngeal Neisseria microbiome ; Timepoint(s) of evaluation of this end point: • Measurement of SBA titre against three Neisseria meningitidis strains: NZ98/254, 5/99 and 44/76-SL (as well as additional strains as indicated) at 5, and 13 months of age in children receiving 4CMenB at 2, 4 and 12 months of age • Measurement of epigenome modifications, potentially including changes in methylation and histone modification DNA • Quantification of 4CMenB antigen-specific antibody secreting cells by ELISPOT at day 7 and day 28 after the 2nd and 3rd doses of 4CMenB vaccine given at 2, 4 and 12 months of age • Analysis of gene expression profiles in PBMCs +/- lymphocyte subsets • Exploratory measurement of plasma proteins. • Investigation of the oro-pharyngeal Neisseria microbiome, at 5 and 13 months in all study children. | — |
Countries
United Kingdom
Contacts
Public ContactOxford Vaccine Group
University of Oxford
Outcome results
None listed