This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We hypothesize that the immunogenicity of heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7), which effectively prevents invasive pneumococcal disease, will vary directly with birth weight in very low birth weight infants (VLBW). Goals Streptococcus pneumoniae causes an estimated 10-25% of all pneumonias in the United States, and is responsible for some 40,000 deaths each year. With the virtual eradication of Haemophilus influenzae type b (Hib) disease in the United States following the introduction of conjugate vaccines, S. pneumoniae has emerged as a leading cause of bacteremia and meningitis in infants. Invasive pneumococcal disease has a peak incidence of 235/100,000 among children aged 6-11 months. Pneumococcal meningitis carries a higher risk of death (15%) or neurologic sequelae (12-28%) than that caused by Hib or Neisseria meningitides. Premature infants are at risk for increased incidence of disease from a variety of pathogens, and for an increased severity of disease if they become infected. Epidemiological information gathered during a recent efficacy trial of a conjugated pneumococcal vaccine suggested that a 2.6-fold increase in invasive pneumococcal disease among infants with birth weights <2500 grams. Although only 133 infants with birth weights less than 1500 grams were included, the rate of disease among unimmunized infants born weighing 1000-1500 grams suggested a 6.7-fold increase in risk over full term infants. The American Academy of Pediatrics (AAP) recommends that 'prematurely born infants, including infants of low birth weight, should be immunized at the usual chronological age in most cases.' However, the AAP also cautions that 'some studies suggest a reduced immune response in VLBW infants (<1500 grams) immunized by the usual schedule.' The responses of premature infants to the current generation of childhood vaccines differ in some important aspects from the responses of infants born at term. Although preterm infants generally respond normally to vaccines given at the same postnatal ages as infants born at term, antibody titers to Hib, polio, and hepatitis B have been reported to be lower by several investigators. The potential for inadequate antibody responses seems to be greatest for the least immunogenic vaccines. In general, infants are relatively poor at mounting the T-cell-independent responses needed to produce immunity to polysaccharide antigens. The conversion of this response to a T-cell-dependent one by conjugating a polysaccharide antigen to an immunogenic protein can produce a successful immune response to the polysaccharide. This strategy has been successfully employed in the production of several vaccines including those against Hib and S. pneumoniae. However, the current conjugate vaccines against S. pneumoniae raise specific concerns for premature infants. Using a variety of conjugate vaccines, data from several studies suggest that even conjugate vaccines may be less immunogenic among sick or extremely premature infants. PCV-7, the heptavalent, conjugate pneumococcal vaccine to be evaluated in this study was developed by Wyeth-Lederle Vaccines and Pediatrics (Rochester, NY). It has been shown to be safe, immunogenic and effective in trials among human infants. PCV-7 is recommended by the manufacturer, the AAP, and the Centers for Disease Control (CDC) and Prevention's Advisory Committee on Immunization Practices (ACIP) for universal administration to infants at 2, 4, 6, and 12-15 months of age. Specific recommendations for premature infants are not mentioned in the guidelines. The current standard of care for preterm infants is to follow the same timetable. This study is designed to evaluate PCV-7 relatively early in the history of its general use with the goal of establishing guidelines for use in premature infants based on specific data rather than extrapolation from studies of infants born at term. Methods Parents will be asked to complete a diary card after doses 1, 2, and 3 to document any reactions. (In some cases, dose 1 will be given before the infant is discharged to home. In those cases the medical record will be used to document any reactions to the vaccine.) Infants with birth weights less than 1500 grams are routinely seen for neurodevelopmental assessment at 18-22.5 months of age in the Infant Development Clinic (IDC). When infants who are enrolled in this study are in the IDC for their 18 month visit, the parents will be asked about the interval medical history to screen for possible invasive bacterial infections and adverse events. Neurodevelopmental outcome data will be collected from the charts of enrolled infants with birth weights of 1000 grams and lower.
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