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Understanding the Immune Response to Meningitis Vaccines

This study has been completed.
Sponsor:
Collaborator:
Novartis Vaccines
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00901940
First received: May 13, 2009
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

The purpose of the study is to evaluate and compare the immune response to two vaccines against 4 related bacteria: meningococcal serogroups A, C, W−135 and Y. These bacteria can cause meningitis and /or septicaemia (blood poisoning). The two vaccines are a protein−polysaccharide conjugate vaccine (MenACWY)and a meningococcal plain polysaccharide vaccine(MenACWY PS). Both vaccines are licensed and are currently used for travellers to areas with a high incidence of invasive meningococcal disease. However, plain polysaccharide vaccines are known to be poorly immunogenic in children and they do not stimulate immunological memory, apart from the serogroup A component. In contrast, a protein-polysaccharide conjugate vaccine against meningococcal serogroups A, C, W−135 and Y has been found to be immunogenic in infants and to be able to induce immunological memory.

The proposed study is a single centre, open−label, randomised, controlled study in 150 healthy adults aged 18−70 years. The participants will be given either 2 injections of the meningococcal protein−polysaccharide conjugate vaccine one month apart, or one injection of the meningococcal plain polysaccharide vaccine followed one month later with an injection of the meningococcal conjugate vaccine. Blood samples will be collected before immunisation and at several time points following immunisations to evaluate the level of meningococcal specific antibody induced by two different vaccination regimes. The data derived from the study will be relevant in determining which of these vaccines should be used in preference in travellers who are receiving immunisation against meningococcal disease before travelling to high risk areas. Additionally, a number of scientific questions regarding the nature of the immune response to the two vaccines (specifically looking at the white blood cells responsible for producing antibodies, known as B cells) and the role of genetic variations in influencing the vaccine recipient's immune response will be addressed in the study.


Condition Intervention Phase
Meningitis
Septicemia
Biological: Meningococcal (Groups A, C, Y and W-135) Conjugate
Biological: Meningococcal polysaccharide A, C, Y and W135 and Menveo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Single Centre Open-Label Randomised Trial of Meningococcal Serogroup ACYW-135 B Cell Response to Primary & Booster Doses of ACWY Conjugate Vaccine & Primary Dose of ACWY Polysaccharide With Booster Dose of ACWY Conjugate in Adults

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • The primary endpoint will be whether the SBA GMT at day 7 following MenACWY is ≥ 30% greater than that observed at day 7 following MenACWY PS. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The measurement of meningococcal serogroup C SBAs (using human complement) at day 7 following the initial immunisation with MenACWY and MenACWY PS. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
  • The measurement of meningococcal serogroup A and C specific SBAs (using human complement) at day 28 following the initial immunisation with MenACWY and MenACWY PS, and at day 7 and day 28 following the 'follow up' immunisation with MenACWY. [ Time Frame: Day 7-28 ] [ Designated as safety issue: No ]
  • Meningococcal serogroup W-135 and Y SBAs will also be performed on a subset of samples obtained at the above timepoints. [ Time Frame: Day 7-28 ] [ Designated as safety issue: No ]
  • The measurement of meningococcal serogroup A, C, W−135 and Y specific memory B cells and plasma B cells at day 7, and memory B cells at day 28 after first immunisation with MenACWY and MenACWY PS, and after the 'follow up' immunisation with MenACWY. [ Time Frame: Day 7-56 ] [ Designated as safety issue: No ]
  • Other assessments of the immune response to MenACWY and MenACWY PS (e.g. measurement of meningococcal serogroup A, C, W-135 and Y specific IgG by ELISA) may also be performed. [ Time Frame: Day 7-56 ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: June 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MenACWY Plain Polysaccharide (ACWY Vax)
The MenACWY Plain Polysaccharide Vaccine, which is already licensed and is used as a travel vaccine, is known as the MenACWY plain polysaccharide (ACWY Vax). Participants in this arm will receive 1 dose of the MenACWY plain polysaccharide (ACWY Vax) and 1 dose of the MenACWY conjugate (MenACWY).
Biological: Meningococcal polysaccharide A, C, Y and W135 and Menveo
1 x 0.5 mL dose of ACWY Vax, 1 x 0.5 mL dose of Menveo
Other Names:
  • ACWY Vax
  • Menveo
Active Comparator: MenACWY conjugate
The MenACWY conjugate vaccine was licensed in the UK in March 2010, and is known as the MenACWY conjugate vaccine (Menveo). Participants in this arm will receive 2 doses of the MenACWY conjugate vaccine.
Biological: Meningococcal (Groups A, C, Y and W-135) Conjugate
2 x 0.5 mL dose
Other Names:
  • MenACWY
  • Menveo

Detailed Description:

In this single centre, open−label, randomised, controlled study of 150 healthy adults aged 18−70 years we will be evaluating the immune response to immunisation with 2 different vaccines against 4 related bacteria known as Neisseria meningitidis serogroups A, C, W−135 and Y. These bacteria (also known as meningococci) can produce meningitis and septicaemia (blood poisoning). The first vaccine, which has been used as a travel vaccine in the UK for several years, is known as the MenACWY plain polysaccharide (MenACWY PS). The other vaccine, known as the MenACWY conjugate vaccine (MenACWY) was licensed in the UK in March 2010 and is now recommended as a travel vaccine by the Department of Health.

In order to evaluate the immune response to these vaccines we will be measuring not only the blood levels of antibodies specific to serogroup A, C, W−135 and Y meningococci, but also the population of white blood cells known as B cells which produce these antibodies. Two forms of these B cells will be measured, the plasma cells (which actively produce antibodies) and memory B cells (which do not produce antibodies but persist in the body and can be stimulated to turn into plasma cells when required).

Participants will be randomised into group I or group II on a 1:1 basis to receive either MenACWY or MenACWY PS. One month later, all participants will receive a booster dose of the MenACWY conjugate vaccine. The ACWY polysaccharide vaccine will be administered subcutaneously, and the MenACWY conjugate vaccine will be given intramuscularly. Each participant will be observed for at least 15 minutes after vaccination for any immediate reactions.

Blood samples will be collected from each participant for analysis prior to each immunisation, 7 days following the first immunisation and 7 and 28 days following the second immunisation. The volume of blood samples obtained at each timepoint will be 20 mLs. Blood will be used for antibody analysis (by ELISA), B cell analysis (by ELISpot)and DNA extraction for genetic analysis.

In summary, participants enrolled in this study will have a total of 5 visits in a period of 2 months. They will receive two doses of the MenACWY conjugate vaccine or one dose of the ACWY polysaccharide vaccine followed by one dose of the MenACWY conjugate vaccine. During this period they will have a total of 5 blood samples taken (5x20mL= 100 mL of blood taken in a 2 month period).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation after the nature of the study has been explained
  • Male or Female, aged 18- 70 years inclusive
  • In good health as determined by:

    • Medical history
    • History-directed physical examination
    • Clinical judgment of the investigator
  • Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
  • Able (in the Investigator's opinion) and willing to comply with all study requirements
  • Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study

Exclusion Criteria:

  • Are unwilling or unable to give written informed consent to participate in the study
  • Have previously received any meningococcal vaccine (this will be confirmed with the participant's general practitioner after enrolment)
  • Have previously been diagnosed with laboratory confirmed meningococcal disease
  • Have a history of any anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component
  • Have a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):

    • Receipt of any immunosuppressive therapy
    • Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroid therapy* (*prednisolone or equivalent for more than two consecutive weeks within the past 3 months).
  • Have a suspected or known HIV infection or HIV related disease
  • Have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months
  • Have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time
  • Have 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
  • Currently 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: NCT00901940

Locations
United Kingdom
University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Novartis Vaccines
Investigators
Principal Investigator: Andrew Pollard, FRCPCH, PhD University of Oxford, Department of Paediatrics
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Andrew Pollard, Chief Investigator, University of Oxford
ClinicalTrials.gov Identifier: NCT00901940     History of Changes
Other Study ID Numbers: 2007/04
Study First Received: May 13, 2009
Last Updated: June 10, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Meningitis
Central Nervous System Diseases
Central Nervous System Infections
Nervous System Diseases

ClinicalTrials.gov processed this record on November 25, 2014