Effect of Two Versus Three Pneumococcal Conjugate Vaccinations
Condition: Streptococcus Pneumoniae Infection
MeSH terms: Pneumonia, Pneumococcal; Pneumococcal Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      Two( 2) or three (3) instead of four vaccinations before the age of 6 months with
      pneumococcal conjugate vaccine are presumed to protect children against invasive pneumococcal
      disease like meningitis, at least on the short term till 18-24 months of age. The current
      hypothesis in this study is 2 or 3 vaccinations will protect against IPD but will not alter
      pneumococcal nasopharyngeal carriage in infants, and consequently not change pneumococcal
      transmission and induce no herd-immunity. Furthermore, antibody development and memory may
      benefit from carriage of vaccine type S. pneumoniae
    

Detailed description: 
      Two(2 and 4 months) and three vaccinations (2,4 and 11 months) with 7-valent pneumococcal
      conjugate vaccine Prevnar in infants are presumed to provide about 90% protection against
      invasive pneumococcal disease (IPD) for vaccine type pneumococci, at least until 18-24 months
      of age. Licensure of the vaccine however is based on studies with 3 vaccinations before 6
      months and a booster vaccination half a year later (3+1 scheme). Cost-effectiveness in
      national infant vaccination programs (NIPs)is much improved by high herd-immunity effects,as
      observed in the USA after licensure of Prevnar in 2000, both for IPD and AOM. However,
      overall pneumococcal carriage reduction (and nasopharyngeal replacement) has not been
      assessed in studies with reduced doses. With reduced carriage reduction, effects on
      respiratory tract infections and herd immunity may be significantly less.

      The primary aim of the current study is to compare effect of 2-doses (at ages 2 and 4 months)
      with a 3-doses scheme(2+1, at 2, 4 and 11 months) on nasopharyngeal pneumococcal carriage and
      replacement and family transmission(sibs and caregivers), in order to allow modelling for
      herd-immunity.

      The secondary aim is to determine the effect of a reduced doses scheme on serum
      antipneumococcal antibody levels at the age of 12 and 24 months.

      A third aim is to determine antipneumococcal antibody levels and memory B-cell development
      after booster vaccination at 24 months of age, after 2 or 2+1 doses and compare these with a
      first vaccination at 24 months of age.

      Opportunities are the determination of nasopharyngeal colonizing pneumococci in unvaccinated
      infants in the Netherlands before implementation of Prevnar in the NIP, evaluation of
      replacing pneumococci in the nasopharynx after vaccinations and analysis of effects on other
      colonizing bacteria like H.influenzae, M. catarrhalis and S.aureus. Furthermore, the relation
      between colonizing pneumococci and serotypes causing IPD in the Netherlands can be evaluated.

      Methods : 1000 infants and families will be included in a randomized,controlled study with 3
      interventions groups

        1. Prevnar at 2 and 4 months

        2. Prevnar at 2, 4 and 11 months

        3. Prevnar at 24 months (controls)

      The children will be followed until 2 years of age with nasopharyngeal swabs for bacterial
      culture before the first vaccination, at 6, 12, 18 and 24 months of age. One sibling and one
      parent/caregiver will be swabbed when the infant is 12 and 24 months. Blood for antibody
      determination will be obtained from 80 children of groups 1 and 2, and from 30 children in
      the control group. Questionnaires on health and respiratory infections and antibiotic
      prescription for RTI will be obtained.

      At 24 months of age, all children of groups 1 and 2 will be offered a booster vaccination.
      Antibody levels will be measured before and 4 weeks after this vaccination at 2 years of age
      in a subset of 80 children per group and compared with 80 children who received a first
      vaccination at 24 months of age.
    

Intervention name(s): PCV7; PCV7
Intervention type(s): Biological; Biological
Intervention description(s): PCV7 at age 2 and 4 months; PCV7 at age 2, 4 and 11 months
Other intervention name(s): Prevenar; Prevenar
Intervention MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: pneumococcal conjugate vaccination; nasopharyngeal carriage; herd immunity; antipneumococcal antibodies; respiratory tract infections; National infant vaccination program