Understanding the Immune Response to Two Different Meningitis Vaccines
A Single Centre, Open-label, Randomised Clinical Study to Investigate Meningococcal Serogroup A and C Saccharide Specific B Cell Responses in Adult Volunteers to One of Three Regimens of Meningococcal ACWY Conjugate Vaccine or Meningococcal ACWY Polysaccharide Vaccine Priming Doses Followed by a Booster Dose of the Meningococcal ACWY Conjugate Vaccine
1 other identifier
interventional
20
1 country
1
Brief Summary
The bacterium (germ) Neisseria meningitidis causes meningitis and blood poisoning. N meningitidis is classified into different serogroups (types), based on its outer polysaccharide (carbohydrate) capsule. Serogroups A,B,C,W \& Y are responsible for the vast majority of meningococcal disease worldwide. Older vaccines against types A,C,W \& Y contain part of the polysaccharide capsule of the germ. However, these polysaccharide vaccines do not provide long-term protection against disease and are less effective in young children, the group most at risk of meningococcal disease. Newer "conjugate" ACWY vaccines attach a polysaccharide to a protein carrier - these provoke a good response in young children and can provide long-term protection. White blood cells called B cells produce antibodies, which are the main components of protection against meningococcal disease. Although many studies have investigated the immune response to these vaccines in different age groups by measuring specific antibodies, there is limited information about the B cells underlying such an immune response. Several different subsets (populations) of B cells exist in the blood. Previous studies by the investigators group suggest that different numbers of B cells are produced in response to each vaccine type. However, little is understood about which subset of B cell is important for antibody production in response to these polysaccharide or conjugate vaccines. This study aims to provide detailed information on the immune response to meningococcal vaccines by investigating the appearance of B cells and their subsets in the blood after vaccination with the polysaccharide and conjugate vaccines. These observations will help us understand how polysaccharide and conjugate vaccines stimulate the immune system in different ways. This knowledge will help in the development of new vaccines that are effective across all age groups. The investigators aim to recruit 20 adults aged 30-70 from Oxfordshire. The study will be funded by the Oxford Vaccine Group.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Dec 2012
Shorter than P25 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 19, 2012
CompletedFirst Posted
Study publicly available on registry
May 8, 2012
CompletedStudy Start
First participant enrolled
December 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2013
CompletedMay 4, 2026
November 1, 2016
4 months
April 19, 2012
April 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
phenotype of meningococcal serogroup A specific B cells
The phenotype of meningococcal serogroup A specific B cells will be observed at day 7 following the initial immunisation with full dose quadrivalent meningococcal polysaccharide vaccine, 1/5th dose quadrivalent meningococcal polysaccharide vaccine and quadrivalent meningococcal conjugate vaccine by Fluorescent Activated Cell Sorting (FACS) analysis. This will be performed at the laboratories of the Oxford Vaccine Group, University of Oxford.
7 days after immunisation
Secondary Outcomes (5)
The phenotype of meningococcal serogroup C specific B cells
28 days after immunisation
The measurement of meningococcal serogroup A and C specific memory B cells
28 days after immunisation
The phenotype of meningococcal serogroup A specific B cells
28 days after immunisation
The phenotype of meningococcal serogroup C specific B cells
7 days after immunisation
The measurement of meningococcal serogroup A and C specific plasma cells
7 days after immunisation
Study Arms (4)
Group 1 Conjugate-conjugate
ACTIVE COMPARATORGroup I will receive 2 doses of the MenACWY-CRM conjugate vaccine (Novartis Vaccines) given 1 month apart. All vaccine doses are 0.5ml and will be administered intramuscularly into the deltoid.
Group 2 Polysaccharide-conjugate
EXPERIMENTALGroup II will receive one full dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later. 0.5 mL of MenACWY-PS vaccine will be administered subcutaneously and 0.5 mL of the MenACWY-CRM vaccine will be administered intramuscularly into the deltoid.
Group 3 Polysaccharide (subcutaneously)-conjugate
EXPERIMENTALGroup III will receive a full dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine subcutaneously, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later.
Group 4: 1/5th dose Polysaccharide:conjugate
EXPERIMENTALGroup IV will receive one fifth dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later. 0.1 mL of MenACWY-PS vaccine will be administered IM and 0.5 mL of the MenACWY-CRM vaccine will be administered intramuscularly into the deltoid.
Interventions
The MenACWY-CRM conjugate vaccine (Menveo, Novartis) is obtained by extemporaneous mixing just before injection of the lyophilized MenA component to be reconstituted with the MenCWY component. This vaccine is to be administered intramuscularly.
To obtain the one-fifth dose of MenACWY-PS, 0.5ml of a full dose of MenACWY-PS will be reconstituted, and then 0.4ml will be discarded prior to subcutaneous injection. The MenACWY-CRM conjugate vaccine (Menveo, Novartis) is obtained by extemporaneous mixing just before injection of the lyophilized MenA component to be reconstituted with the MenCWY component. This vaccine is to be administered intramuscularly.
The MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) is obtained by reconstituting the purified ACWY polysaccharides with the 0.5 ml water for injection. This vaccine should be administered subcutaneously.The MenACWY-CRM conjugate vaccine (Menveo, Novartis) is obtained by extemporaneous mixing just before injection of the lyophilized MenA component to be reconstituted with the MenCWY component. This vaccine is to be administered intramuscularly.
The MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) is obtained by reconstituting the purified ACWY polysaccharides with the 0.5 ml water for injection.The MenACWY-CRM conjugate vaccine (Menveo, Novartis) is obtained by extemporaneous mixing just before injection of the lyophilized MenA component to be reconstituted with the MenCWY component. This vaccine is to be administered subcutaneously
Eligibility Criteria
You may qualify if:
- Participants must meet the following conditions in order to be enrolled:
- Between 30 and 70 years of age inclusive;
- Willing and able to give informed consent for participation after the nature of the study has been explained;
- In good health as determined by:
- medical history history-directed physical examination clinical judgment of the investigator
- Able (in the Investigators opinion) and willing to comply with all study requirements including be available for all the visits scheduled in the study;
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
You may not qualify if:
- Participants with any of the following conditions or characteristics will be excluded from study enrolment:
- Prior receipt of a meningococcal vaccine;
- Prior laboratory confirmed disease caused by N meningitides;
- Prior history of any anaphylactic shock, asthma, urticarial or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component;
- Known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):
- Receipt of immunostimulants
- Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding year or long-term systemic corticosteroid therapy (prednisolone or equivalent for more than two consecutive weeks within the past 3 months).
- Suspected or known HIV infection or HIV related disease;
- Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months
- Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
- Any condition, which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
- Participation in another clinical trial investigating a vaccine, a drug, a medical device, or a medical procedure;
- Pregnancy as confirmed by a positive pregnancy test ;
- Concurrent breast-feeding.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Oxford Vaccine Group
Oxford, Oxfordshire, OX3 7LE, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew J Pollard, BA, MBBS, FRCPCH, PhD
University of Oxford
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 19, 2012
First Posted
May 8, 2012
Study Start
December 1, 2012
Primary Completion
April 1, 2013
Study Completion
April 1, 2013
Last Updated
May 4, 2026
Record last verified: 2016-11