Fractional Dose Tetravalent A, C, Y, W135 Meningococcal Polysaccharide Vaccine
Condition: Infections, Meningococcal; Meningitis, Meningococcic
MeSH terms: Meningococcal Infections; Meningitis, Meningococcal; Meningitis
Study type: Interventional
Phase: Phase 4

Summary: 
      Hypothesis:

      Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could
      confer a similar functional immunogenic response as the dose of 50 μg currently being used,
      and subsequently be equally protective.

      The purpose of this study is to evaluate the use of fractional dose tetravalent meningococcal
      polysaccharide vaccine to control outbreak especially caused by N. meningitidis serogroup
      W135

      Primary Objectives:

        -  To measure the immunogenicity of a dose corresponding to one fifth of the amount of the
           licensed meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 10 μg for each component;
           and

        -  To measure the immunogenicity of a dose corresponding to one tenth of the licensed
           meningococcal A/C/Y/W135 polysaccharide vaccine, i.e. 5 μg for each component.
    

Detailed description: 
      In 2002, an epidemic of meningococcal disease started in Burkina Faso and Neisseria
      meningitidis serogroup W135 was identified as the causative organism. This event followed the
      outbreaks of 2000 and 2001 in Mecca, Saudi Arabia, and was the first large epidemic caused by
      serogroup W135. Mass vaccination of the population with the only vaccine protecting against
      W135, i.e. the tetravalent A/C/Y/W135 polysaccharide vaccine (TPSV), was not possible because
      of the global shortage in supply, in addition to its cost. In 2003, GlaxoSmithKline (GSK)
      produced a trivalent polysaccharide vaccine A/C/W135 for US$ 1.5. This vaccine was used in
      Burkina Faso in the new epidemic faced by this country in 2003. However, availability and
      affordability of the tetravalent A/C/Y/W135 polysaccharide vaccine and of the trivalent
      A/C/W135 polysaccharide vaccine are still under discussion between the WHO and the producers.
      The risk of further epidemics due to the W135 strain in other African countries is of high
      concern for the scientific community.

      The current dose of the licensed tetravalent A/C/Y/W135 polysaccharide vaccine contains 50 μg
      of each polysaccharide component. During the 1980's, researchers from the Walter Reed Army
      Institute of Research (WRAIR) did extensive works on the immunogenicity of meningococcal
      polysaccharide vaccines in adults. A first study performed by Griffiss et al. demonstrated
      that doses of 5 μg of group Y and group W135 polysaccharides were as effective as doses of 50
      μg in inducing production of bactericidal antibody amounts correlating with functional
      immunity (Griffiss et al. Mil Med 1985; 150: 529-33). A second study concluded that doses of
      7.5 μg (Y and W) and 15 μg (A and C) were sufficient to induce equivalent binding and
      bactericidal antibody responses as 50 μg (Griffiss et al. Infect Immun 1982; 37: 205-8). In a
      more recent study from Granoff et al., 1/50 (1 mcg) of the ordinary dose of tetravalent
      A/C/Y/W135 vaccine was given (Granoff et al. J Infect Dis 1998; 178: 870-4). The antibody
      responses to A and C have been measured, and this low dose was sufficient to mount a C
      response in most of the subjects, but the dose was less effective in eliciting a response to
      A. The antibody responses to W135 and Y were not reported.

      Hypothesis:

      Lower doses of each A/C/Y/W135 component of the meningococcal polysaccharide vaccine could
      confer a similar functional immunogenic response as the dose of 50 μg currently being used,
      and subsequently be equally protective.

      It would potentially bring two major benefits. Firstly, it would increase the number of
      tetravalent vaccine doses available on the market. Secondly, it would decrease the cost of
      the individual vaccine dose. As a result, more people could be vaccinated, and thereby
      protected against the disease, and to a lower price.

      Results obtained with the study on the tetravalent A/C/Y/W135 polysaccharide vaccine would be
      valid for the trivalent A/C/W135 polysaccharide vaccine.
    

Intervention name(s): A, C, Y, W135 meningococcal polysaccharide vaccine
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single
Primary purpose: Prevention
Keywords: Meningitis; Dose-Response Relationship, Immunologic; Neisseria meningitidis; Outbreaks; Vaccine; Africa; Uganda; Prevention of Neisseria meningitidis infections; In outbreak contexts in developing countries