Meningococcal VaccinesNCT02398396
Investigating Meningococcal Vaccines in Adults
A study testing 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics in people with Meningococcal Vaccines and Meningococcal Infections, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This study will be an open label, exploratory immunogenicity study conducted by the Oxford Vaccine Group, University of Oxford. This study will investigate the breadth of protective activity of serum anti-FHbp antibody responses of adults immunized with 4CMenB (Bexsero®) vaccine as well as investigating the nature of… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Meningococcal Vaccines, Meningococcal Infections, Neisseria Meningitidis
- What is being tested?
- 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2015to 13 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years to 60 years inclusive on the day of first vaccination.
- To be in good health as determined by medical history, physical examination and clinical judgment of the investigators.
- Agree (in the Investigator's opinion) to comply with all study requirements
- Agree to allow his or her General Practitioner (and/or Consultant if appropriate), to be notified of participation in the study
- Agree to provide their National Insurance/Passport number for the purposes of TOPS registration and bank account information for the purpose of reimbursement for the duration of their participation.
Who cannot join
- Have any known or suspected impairment or alteration of immune function, resulting from, for example:
- Congenital or acquired immunodeficiency (including IgA deficiency)
- Human Immunodeficiency Virus (HIV) infection or symptoms/signs suggestive of an HIV-associated condition
- Autoimmune disease
- Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid therapy.
- Chronic illness that could interfere with immunological function or donation of the required volumes of blood (e.g. cardiac or renal disease, diabetes, or auto-immune disorders).
Show all 20Show fewer
- Receipt of a live vaccine within 4 weeks prior to vaccination or a killed vaccine within 7 days prior to vaccination.
- History of group B meningococcal vaccination
- Have received a dose of a meningococcal groups A, C, W, Y conjugate vaccine within 30 days of enrolment or wish to receive a dose of this vaccine during the study period.
- Plan to receive any vaccine other than the study vaccine within 4 weeks following vaccination.
- History of severe allergic reaction after vaccination or known hypersensitivity to any vaccine component
- History of meningococcal disease
- Receipt of blood, blood products, or plasma derivatives within the past 3 months.
- Recent significant blood donation (e.g., to the National Blood Service) within 8 weeks of enrolment, or plans to donate blood during the study period.
- Thrombocytopenia or any bleeding disorder.
- Pregnancy as confirmed by a positive pregnancy test, or currently breastfeeding.
- Enrolled in another study, which, in the opinion of the investigator, could compromise the integrity of either study being conducted.
- A member of staff on the delegation log
- According to the TOPS database, have recently taken part in a significant number of other studies, which, in the opinion of the investigator, warrant exclusion from further studies.
- Have any condition, which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Oxford, Oxfordshire, OX3 7LE
About this study
Official title: Investigating Meningococcal Vaccines in Adults - An Exploratory, Open-label, Immunogenicity Study of a Licensed Meningococcal Capsular Group B Vaccine (4CMenB, Bexsero®) in Adults
This study will be an open label, exploratory immunogenicity study conducted by the Oxford Vaccine Group, University of Oxford. This study will investigate the breadth of protective activity of serum anti-FHbp antibody responses of adults immunized with 4CMenB (Bexsero®) vaccine as well as investigating the nature of the B-cell and T-cell responses induced by vaccination.
The investigators aim to enroll 15 to 20 healthy adults aged 18 to 60, who will be immunized with two doses of 4CMenB (Bexsero®) two months apart according to the licensed schedule. Blood samples will be obtained at baseline and after each dose of vaccine.
Read the detailed description
Neisseria meningitidis (N. meningitidis, meningococcus) is a leading cause of bacterial meningitis and septicaemia worldwide. The introduction of serotype specific glycoconjugate vaccines into the routine infant immunization schedule, in countries such as the United Kingdom, has led to dramatic reductions in the burden of disease. The development of effective vaccines against capsular group B N. meningitidis has long been an unmet need and has necessitated the development of novel approaches to vaccine design. In 2013, the first capsular group B meningococcal vaccine was licensed in the UK. The new vaccine (4CMenB, trade name Bexsero ®), is manufactured by Novartis Vaccines and contains four components - a recombinant Factor H binding protein (FHbp), Neisseria meningitidis capsular group B Neisseria Heparin Binding Antigen (NHBA) fusion protein, recombinant Neisseria meningitidis group B Neisserial adhesin A (NadA) protein and Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254 containing PorA P1.4. This multicomponent vaccine is also referred to as the "four component meningococcal B" or "4CMenB" vaccine.
Factor H binding protein is an important virulence factor expressed on the surface of N. meningitidis and is a key component of the 4CMenB vaccine. It has been established that the function of FHbp is to bind human complement factor H, whose physiological function in turn is to act as an important down-regulator of the host alternative complement pathway. Binding of human factor H to the bacterial surface via FHbp is thought to interfere with complement mediated lysis and is an important immune evasion strategy of N. meningitidis. Consequently, FHbp is a logical target for a protective vaccine against capsular group B N. meningitidis.
There remain several gaps in our knowledge about the underlying mechanisms by which human antibodies to FHbp elicit complement mediated bactericidal activity. In humans immunised with vaccines containing FHbp, the antigen (FHbp) is expected to form a complex with human factor H. The precise epitopes targeted by anti-FHbp antibodies in vaccinees have not been fully elucidated. Conceivably, the formation of a FHbp-factor H complex following vaccination may prevent the exposure of key FHbp epitopes. Therefore, it is not known whether the interaction between FHbp and human Factor H affects the bactericidal activity of antibodies produced following vaccination with 4CMenB.
This study will investigate the breadth of protective activity of serum anti-FHbp antibody responses of adults immunized with 4CMenB (Bexsero®) vaccine as well as investigating the nature of the B-cell and T-cell responses induced by vaccination.
We aim to enroll 15 to 20 healthy adults aged 18 to 60, who will be immunized with two doses of 4CMenB (Bexsero®) two months apart according to the licensed schedule. Sera will be obtained at baseline and after each dose of vaccine, which will be assayed for IgG antibody responses to FHbp by ELISA, as well as for bactericidal activity against a panel of genetically diverse meningococcal strains and for the ability to inhibit binding of FH to FHbp. Other assays for meningococcal immunity may also be performed such as antibody binding to live bacteria measured by flow cytometry, and the ability of the serum antibodies to confer passive protection in an infant rat bacteraemia model. Laboratory analyses to quantify the B- and T-cell responses specific to the 4CMenB vaccine will be performed using peripheral blood mononuclear cells (PBMCs) derived from study participants sampled before, and after each dose. We will also explore whether the formation of the FH-FHbp complex results in the generation of cross-reactive antibodies directed against Factor H.
This will be the first study in humans to explore in detail the anti-FHbp characteristics generated following immunization with 4CMenB (Bexsero®) and offers a unique opportunity to use a licensed vaccine to improve our understanding of how to induce efficient protective responses. It is hoped that the results obtained from this study will contribute to our understanding of the host response to vaccination against capsular group B N. meningitidis.
- Conditions
- Meningococcal Vaccines, Meningococcal Infections, Neisseria Meningitidis, Factor H-binding Protein, Neisseria Meningitidi
- Being tested
- 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics
- Medical subject headings
- Meningococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4CMenB (Bexsero®) - Novartis Vaccines and DiagnosticsBiological
4CMenB vaccine (Bexsero - Novartis Vaccines and Diagnostics) 0.5ml intra-muscularly; two doses, administered 2 months apart. Each dose of vaccine contains recombinant Neisseria meningitidis group B NHBA fusion protein (50 micrograms); recombinant Neisseria meningitidis group B NadA protein (50 micrograms); recombinant Neisseria meningitidis group B FHbp fusion protein (50 micrograms) and Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254 (25 micrograms measured as amount of total protein containing the PorA P1.4)
| Study group | Role | What they receive |
|---|---|---|
| Open Label: 4CMenB (Bexsero®) | Experimental | Not described Receives: Biological: 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterise the breadth of protective activity of serum anti-FHbp antibody responses of adults immunised with 4CMenB (Bexsero) vaccine
As measured by IgG antibody responses to FHbp as measured by serum bactericidal activity against a panel of genetically diverse meningococcal strains
Measured: 3 months
Secondary outcomes (3)
To investigate the nature of the B-cell response that supports the induction of antibody with functional activity following vaccination with 4CMenB
Quantification of circulating vaccine-induced memory B-cells specific for vaccine antigens before and after each, dose.
Measured: 3 months
To investigate the nature of the T-cell response that supports the induction of antibody with functional activity following vaccination with 4CMenB
Quantification of vaccine-induced, antigen specific T-cell responses and associated cytokine production before and after each dose.
Measured: 3 months
Determine whether adults immunised with 4CMenB develop serum IgG and IgM antibodies to human FH
Serum IgG and IgM antibodies to human FH will as measured by ELISA
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study startApr 2015
- Primary completionNov 2015
- Study completion13 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Meningococcal VaccinesStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02398396
- Sponsor's protocol ID
- OVG 2014/12
- Status last verified
- Oct 2018
- First submitted
- 20 Mar 2015
- Last updated
- 27 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Giuntini S, Lujan E, Gibani MM, Dold C, Rollier CS, Pollard AJ, Granoff DM. Serum Bactericidal Antibody Responses of Adults Immunized with the MenB-4C Vaccine against Genetically Diverse Serogroup B Meningococci. Clin Vaccine Immunol. 2017 Jan 5;24(1):e00430-16. doi: 10.1128/CVI.00430-16. Print 2017 Jan.
PubMed 27847367
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Meningococcal Vaccines in Adults - An Exploratory, Open-label, Immunogenicity Study of a Licensed Meningococcal Capsular Group B Vaccine (4CMenB, Bexsero®) in Adults
- ClinicalTrials.gov ID
- NCT02398396
- Acronym / sponsor ID
- OVG 2014/12
- Conditions
- Meningococcal Vaccines, Meningococcal Infections, Neisseria Meningitidis, Factor H-binding Protein, Neisseria Meningitidi
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- 13 Jun 2019 (actual)
- First posted
- 25 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be an open label, exploratory immunogenicity study conducted by the Oxford Vaccine Group, University of Oxford. This study will investigate the breadth of protective activity of serum anti-FHbp antibody responses of adults immunized with 4CMenB (Bexsero®) vaccine as well as investigating the nature of the B-cell and T-cell responses induced by vaccination.
The investigators aim to enroll 15 to 20 healthy adults aged 18 to 60, who will be immunized with two doses of 4CMenB (Bexsero®) two months apart according to the licensed schedule. Blood samples will be obtained at baseline and after each dose of vaccine.
Detailed description
Neisseria meningitidis (N. meningitidis, meningococcus) is a leading cause of bacterial meningitis and septicaemia worldwide. The introduction of serotype specific glycoconjugate vaccines into the routine infant immunization schedule, in countries such as the United Kingdom, has led to dramatic reductions in the burden of disease. The development of effective vaccines against capsular group B N. meningitidis has long been an unmet need and has necessitated the development of novel approaches to vaccine design. In 2013, the first capsular group B meningococcal vaccine was licensed in the UK. The new vaccine (4CMenB, trade name Bexsero ®), is manufactured by Novartis Vaccines and contains four components - a recombinant Factor H binding protein (FHbp), Neisseria meningitidis capsular group B Neisseria Heparin Binding Antigen (NHBA) fusion protein, recombinant Neisseria meningitidis group B Neisserial adhesin A (NadA) protein and Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254 containing PorA P1.4. This multicomponent vaccine is also referred to as the "four component meningococcal B" or "4CMenB" vaccine.
Factor H binding protein is an important virulence factor expressed on the surface of N. meningitidis and is a key component of the 4CMenB vaccine. It has been established that the function of FHbp is to bind human complement factor H, whose physiological function in turn is to act as an important down-regulator of the host alternative complement pathway. Binding of human factor H to the bacterial surface via FHbp is thought to interfere with complement mediated lysis and is an important immune evasion strategy of N. meningitidis. Consequently, FHbp is a logical target for a protective vaccine against capsular group B N. meningitidis.
There remain several gaps in our knowledge about the underlying mechanisms by which human antibodies to FHbp elicit complement mediated bactericidal activity. In humans immunised with vaccines containing FHbp, the antigen (FHbp) is expected to form a complex with human factor H. The precise epitopes targeted by anti-FHbp antibodies in vaccinees have not been fully elucidated. Conceivably, the formation of a FHbp-factor H complex following vaccination may prevent the exposure of key FHbp epitopes. Therefore, it is not known whether the interaction between FHbp and human Factor H affects the bactericidal activity of antibodies produced following vaccination with 4CMenB.
This study will investigate the breadth of protective activity of serum anti-FHbp antibody responses of adults immunized with 4CMenB (Bexsero®) vaccine as well as investigating the nature of the B-cell and T-cell responses induced by vaccination.
We aim to enroll 15 to 20 healthy adults aged 18 to 60, who will be immunized with two doses of 4CMenB (Bexsero®) two months apart according to the licensed schedule. Sera will be obtained at baseline and after each dose of vaccine, which will be assayed for IgG antibody responses to FHbp by ELISA, as well as for bactericidal activity against a panel of genetically diverse meningococcal strains and for the ability to inhibit binding of FH to FHbp. Other assays for meningococcal immunity may also be performed such as antibody binding to live bacteria measured by flow cytometry, and the ability of the serum antibodies to confer passive protection in an infant rat bacteraemia model. Laboratory analyses to quantify the B- and T-cell responses specific to the 4CMenB vaccine will be performed using peripheral blood mononuclear cells (PBMCs) derived from study participants sampled before, and after each dose. We will also explore whether the formation of the FH-FHbp complex results in the generation of cross-reactive antibodies directed against Factor H.
This will be the first study in humans to explore in detail the anti-FHbp characteristics generated following immunization with 4CMenB (Bexsero®) and offers a unique opportunity to use a licensed vaccine to improve our understanding of how to induce efficient protective responses. It is hoped that the results obtained from this study will contribute to our understanding of the host response to vaccination against capsular group B N. meningitidis.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label: 4CMenB (Bexsero®) | Experimental | Biological: 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years to 60 years inclusive on the day of first vaccination.
- To be in good health as determined by medical history, physical examination and clinical judgment of the investigators.
- Agree (in the Investigator's opinion) to comply with all study requirements
- Agree to allow his or her General Practitioner (and/or Consultant if appropriate), to be notified of participation in the study
Key exclusion criteria (20 listed)
- Have any known or suspected impairment or alteration of immune function, resulting from, for example:
- Receipt of a live vaccine within 4 weeks prior to vaccination or a killed vaccine within 7 days prior to vaccination.
- History of group B meningococcal vaccination
- Have received a dose of a meningococcal groups A, C, W, Y conjugate vaccine within 30 days of enrolment or wish to receive a dose of this vaccine during the study period.
- Plan to receive any vaccine other than the study vaccine within 4 weeks following vaccination.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics4CMenB vaccine (Bexsero - Novartis Vaccines and Diagnostics) 0.5ml intra-muscularly; two doses, administered 2 months apart. Each dose of vaccine contains recombinant Neisseria meningitidis group B NHBA fusion protein (50 micrograms); recombinant Neisseria meningitidis group B NadA protein (50 micrograms); recombinant Neisseria meningitidis group B FHbp fusion protein (50 micrograms) and Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254 (25 micrograms measured as amount of total protein containing the PorA P1.4) | Biological | Open Label: 4CMenB (Bexsero®) |
Primary outcome
To characterise the breadth of protective activity of serum anti-FHbp antibody responses of adults immunised with 4CMenB (Bexsero) vaccine
Time frame: 3 months
As measured by IgG antibody responses to FHbp as measured by serum bactericidal activity against a panel of genetically diverse meningococcal strains
3 secondary outcomes
To investigate the nature of the B-cell response that supports the induction of antibody with functional activity following vaccination with 4CMenB
Time frame: 3 months
To investigate the nature of the T-cell response that supports the induction of antibody with functional activity following vaccination with 4CMenB
Time frame: 3 months
Determine whether adults immunised with 4CMenB develop serum IgG and IgM antibodies to human FH
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2021.
- Derived from this study: PubMed 27847367Giuntini S, Lujan E, Gibani MM, Dold C, Rollier CS, Pollard AJ, Granoff DM. Serum Bactericidal Antibody Responses of Adults Immunized with the MenB-4C Vaccine against Genetically Diverse Serogroup B Meningococci. Clin Vaccine Immunol. 2017 Jan 5;24(1):e00430-16. doi: 10.1128/CVI.00430-16. Print 2017 Jan.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 4CMenB (Bexsero®) - Novartis Vaccines and Diagnostics in people with Meningococcal Vaccines and Meningococcal Infections, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterise the breadth of protective activity of serum anti-FHbp antibody responses of adults immunised with 4CMenB (Bexsero) vaccine (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02398396, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2021.