Multicenter Pilot Study Evaluating the Immunogenicity of an Innovative Pneumococcal Vaccination Strategy in Splenectomized Adults
Condition: Splenectomized Patients
Study type: Interventional
Phase: Phase 2

Summary: 
      Evaluate the immunogenicity of an innovative pneumococcal vaccination strategy in
      splenectomized adults comprising 1 dose of Prevenar13® conjugate vaccine (PCV) at M0 followed
      by 1 dose of Pneumo23® or Pneumovax® polysaccharide vaccine (PPSV) at M2. Duration of
      follow-up of 36 months.

      The main endpoint will be the proportion of subjects responsive to 9 of the 13 serotypes
      common to the PCV and PPSV vaccines, selected because of their frequency in invasive
      infections in adults in France and their potentially reduced susceptibility to penicillin
      (serotypes 1, 3, 6A, 7F, 9V, 14, 19A, 19F, 23F).
    

Detailed description: 
      The splenectomized patient is more susceptible to infections because of the lack of specific
      response to the polysaccharide antigens that compose the capsules of certain bacteria. These
      very severe infections are known as Overwhelming Post Splenectomy Infections, or OPSI; they
      are characterized by very rapid onset with no prodrome and carry a high mortality rate. The
      annual incidence of OPSI is estimated at 0.23-0.42% with a lifetime risk of 5%. The role of
      pneumococcus in particular has been clearly established in these infections.

      The most effective strategy to minimize the risk of pneumococcal infection is pneumococcal
      vaccination. Currently there are two types of vaccines available in France: polysaccharide
      and conjugate, both of which induce the production of anti-capsular IgG with both
      neutralizing and opsonic activity.

      Since one of the consequences of asplenia is the absence of IgM production elicited by a
      polysaccharide challenge, due to an absence of splenic B cells, it is difficult to imagine
      that such patients would mount a satisfactory immune response to PPSV vaccination. And in
      fact, several studies have described the occurrence of pneumococcal OPSI in patients who were
      correctly vaccinated.

      The study hypothesis is that a vaccination strategy combining PCV vaccine followed by PPSV
      vaccine will induce a good immune response in splenectomized patients, with good
      tolerability. All available data suggest that the optimum schedule consists of a
      primovaccination with one dose of PCV followed two months later by one dose of PPSV, in order
      to achieve a T-dependent memory response to the 13 serotypes common to the two vaccines.

      The proposed endpoint is therefore to evaluate the immunogenicity and safety of a vaccination
      strategy comprising priming with one dose of Prevenar13® PCV vaccine (serotypes 4, 6B, 9V,
      14, 18C, 19F, 23F, + 1, 3, 5, 6A, 7F, 19A) to induce a T cell memory response, followed by
      the classical administration of one dose of Pneumo23® or Pneumovax® vaccine (serotypes 1, 2,
      3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F).
      Secondary endpoints will evaluate the safety of this strategy in terms of post-immunization
      local and systemic side effects, frequency of invasive pneumococcal infections, predictors of
      immunogenicity, and persistence of immunogenicity 30 months post-immunization.
    

Intervention name(s): Prime-boost pneumococcal immunization
Intervention type(s): Biological
Intervention description(s): 2 months between the 2 vaccines
Other intervention name(s): Prevenar13® followed by Pneumo23®
Intervention MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Pneumococcal infection; Splenectomized; vaccination