Understanding the Immune Response to Two Different Meningitis Vaccines

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01593514
First received: April 19, 2012
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Meningitis
Meningococcal Disease
Septicaemia
Biological: MenACWY-CRM conjugate vaccine (Menveo, Novartis)
Biological: MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis)
Biological: MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis)
Biological: 1/5th dose MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis)
Biological: Polysaccharide (subcutaneously)-conjugate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • phenotype of meningococcal serogroup A specific B cells [ Time Frame: 7 days after immunisation ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The phenotype of meningococcal serogroup C specific B cells [ Time Frame: 28 days after immunisation ] [ Designated as safety issue: No ]
    The phenotype of meningococcal serogroup C specific B cells will be observed at day 28 following the initial immunisation with full dose quadrivalent meningococcal polysaccharide vaccine, 1/5th dose quadrivalent meningococcal polysaccharide vaccine and quadrivalent meningococcal conjugate vaccine using flow cytometry.

  • The measurement of meningococcal serogroup A and C specific memory B cells [ Time Frame: 28 days after immunisation ] [ Designated as safety issue: No ]
    The measurement of meningococcal serogroup A and C specific memory B cells at day 28 following the initial immunisation with full dose quadrivalent meningococcal polysaccharide vaccine, 1/5th dose Quadrivalent meningococcal polysaccharide vaccine or quadrivalent meningococcal conjugate vaccine, and after the booster immunisation with the conjugate vaccine.

  • The phenotype of meningococcal serogroup A specific B cells [ Time Frame: 28 days after immunisation ] [ Designated as safety issue: No ]
    The phenotype of meningococcal serogroup A specific B cells will be observed at day 28 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.

  • The phenotype of meningococcal serogroup C specific B cells [ Time Frame: 7 days after immunisation ] [ Designated as safety issue: No ]
    The phenotype of meningococcal serogroup C 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 using flow cytometry.

  • The measurement of meningococcal serogroup A and C specific plasma cells [ Time Frame: 7 days after immunisation ] [ Designated as safety issue: No ]
    The measurement of meningococcal serogroup A and C specific plasma cells at day 7 following the initial immunisation with full dose quadrivalent meningococcal polysaccharide vaccine, 1/5th dose Quadrivalent meningococcal polysaccharide vaccine or quadrivalent meningococcal conjugate vaccine, and after the booster immunisation with the conjugate vaccine.


Estimated Enrollment: 15
Study Start Date: December 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1 Conjugate-conjugate
Group 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.
Biological: MenACWY-CRM conjugate vaccine (Menveo, Novartis)
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.
Experimental: Group 2 Polysaccharide-conjugate

Group 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.

Biological: MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis)
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.
Experimental: Group 3 Polysaccharide (subcutaneously)-conjugate
Group 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.
Biological: MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis)
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.
Biological: 1/5th dose MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis)
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.
Experimental: Group 4: 1/5th dose Polysaccharide:conjugate

Group 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.

Biological: Polysaccharide (subcutaneously)-conjugate
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593514

Locations
United Kingdom
Oxford Vaccine Group
Oxford, Oxfordshire, United Kingdom, OX3 7LE
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Andrew J Pollard, BA, MBBS, FRCPCH, PhD University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01593514     History of Changes
Other Study ID Numbers: OVG 2012/02
Study First Received: April 19, 2012
Last Updated: August 12, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Vaccines
Meningitis
Meningococcal

Additional relevant MeSH terms:
Meningitis
Meningococcal Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Lactitol
Cathartics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014