Pneumococcal Vaccination of Fiji Infants
Condition: Pneumococcal Infections
MeSH terms: Pneumococcal Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      Pneumonia is the most common reason for admission of Fijian children to hospitals. The most
      common germ causing pneumonia is "streptococcus pneumoniae." It is a common cause of
      meningitis (infection around the brain and spinal cord), ear infections, and blood infections
      and it lives in the nose of humans. A vaccine has been developed that will help prevent these
      common diseases but prevents only about one quarter of pneumonia cases and it is expensive.
      This study explores new ways of giving this vaccine that are affordable, safe, and effective
      in countries such as Fiji. About 550 Fijian infants presenting at 6 weeks of age, for their
      first diptheria, tetanus, toxoid, pertussis vaccine immunization, to one of the participating
      Health Centers or Colonial War Memorial Hospital in urban Suva, Fiji will be enrolled.
      Children will remain in the study for 2 years. Study procedures include full vaccination
      against 7 types of pneumococcus, blood tests, and nasal swabs.
    

Detailed description: 
      This research project began as a study of alternative strategies for Pnc (Pneumococcus)
      immunization for children in developing countries. In the original study, infants presenting
      to a health center in urban Fiji were randomized to receive 1, 2, or 3 doses of PCV (Prevnar)
      followed by a dose of 23-valent PPS (Pneumococcal polysaccharide vaccine) at 6 or 9 months of
      age. The regimens were compared with each other and with 2 control groups with respect to
      immunogenicity, impact on carriage of vaccine type Pnc, and response to a small dose of PPS
      at 15 months of age. After the trial was underway and 228 infants had been recruited,
      concerns were raised about the safety of PPS in infancy. Specifically concerns were raised
      that it might result in later immunological hyporesponsiveness in some of the recipients, to
      some of the serotypes. After a thorough review it was decided to proceed with the study, but
      to modify it so that it addressed directly the issue of potential hyporesponsiveness, while
      not giving PPS to any children under 12 months of age. This protocol represents the
      completion of the study with the new design for the children already enrolled, and a new
      design for a further cohort of children who will be enrolled. The newly designed trial will
      be a single blind, open-label, randomized, controlled trial of 550 healthy infants. Infants
      will be randomized to 1 of 8 equal groups to receive 0, 1, 2, or 3 doses of PCV (Pneumococcal
      conjugate vaccine), with or without a booster of PPS at 12 months of age. Two control groups
      will be recruited, 1 will receive no PCV in infancy and the other will receive a dose of PPS
      at 12 months of age. At 18 months of age, all infants will receive a 20 percent dose of PPS
      to stimulate and allow the assessment of immunological memory. At 2 years of age, any child
      who has received no or one dose of PCV (Groups E, F, G and H) will receive a single dose of
      PCV. Blood samples will be taken at 18 weeks age, 12 months of age, before the 18 months dose
      and 4 weeks later. In addition half of the children will have a blood sample taken at 9
      months and the other half will have a sample taken 2 weeks after their 12 month dose of PPS.
      The 9- and 12-month blood sample will assess the long-term persistence of circulating
      antibody and avidity maturation following a 1, 2, or 3 dose primary series of PCV. The
      primary objective is to demonstrate noninferiority at 19 months of age, of those groups
      receiving PPS at 12 months and those who do not with respect to the proportion of children in
      each group, with a satisfactory immune response at 19 months of age, measured by OPA to each
      of the 11 serotypes included in the PPS for which an OPA has been developed. The secondary
      objective is to assess the immunogenicity and impact on carriage of various Pnc vaccination
      regimens that combine 1 to 3 doses of PCV with a dose of PPS, concerns regarding the
      potential for the development of hyporesponsiveness. Endpoints to be evaluated will include
      serotype specific immunoglobulin G antibody measured by enzyme-linked immunosorbent assay to
      the 23 serotypes in the PPS, avidity assays to the same serotypes, opsonophagocytic assays to
      the 11 serotypes for which these assays are currently available, and Pnc carriage by
      serotype. With hyporesponsiveness as the primary endpoint of interest a scheme of analysis
      has been proposed which will require a minimum sample size of 500.
    

Intervention name(s): Pneumovax 23; Prevnar
Intervention type(s): Biological; Biological
Intervention description(s): 23-valent PPS, 25 micrograms/serotype; 7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Intervention MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Pneumococcal infections; Fiji; infants; vaccine