Understanding the Immune Response to Meningitis Vaccines
Condition: Meningitis; Septicemia
MeSH terms: Sepsis; Meningitis
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

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).
    

Intervention name(s): Meningococcal (Groups A, C, Y and W-135) Conjugate; Meningococcal polysaccharide A, C, Y and W135 and Menveo
Intervention type(s): Biological; Biological
Intervention description(s): 2 x 0.5 mL dose; 1 x 0.5 mL dose of ACWY Vax, 1 x 0.5 mL dose of Menveo
Other intervention name(s): MenACWY; Menveo; ACWY Vax; Menveo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention