Immunogenicity of PCV-7 Vaccine in VLBW Infants

Streptococcus pneumoniae causes an estimated 10-25% of all pneumonias in the United States,
and is responsible for an estimated 40,000 deaths per year. 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 neurodevelopmental impairment (12-28%) than Hib or
Neisseria meningitides.

Premature infants are at a higher risk for invasive disease with Streptococcus pneumoniae.
The heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7) effectively prevents invasive
pneumococcal disease in full-term infants, but was been incompletely studied in premature
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", but cautions that "some studies suggest a reduced immune response in very
low-birth-weight infants (<1500 g)."

This observational study assessed the effectiveness of the PCV-7 vaccine to generate a
sufficient immune response in a safe manner when given to very low birth weight (VLBW)
infants in routine pediatric practice. We hypothesized that among VLBW infants, the frequency
of estimated minimum protective antibody titers to PCV-7 (>=0.15 μg/mL) would decrease with
decreasing birth weight.

Infants 501-1500g birth weight and <32 0/7 weeks gestational age were enrolled from nine
NICHD Neonatal Research Network centers from 2004 to 2006. Enrollment was stratified by
weight group to yield approximately 20 infants per 100g increments from 501-1500g birth
weight whose primary PCV-7 series was initiated before 3 months and completed by 8 months
after birth. The infants' primary providers gave PCV-7 vaccination at 2, 4, and 6 months
after birth. Infants had a single 2-ml blood sample drawn 4-6 weeks following the third dose
of PCV-7. Antibodies for each of the seven vaccine serotypes included in PCV-7 were measured
by enzyme-linked immunosorbent assay. Children were followed until 18-22 months corrected age
to assess survival, infection, and neurodevelopmental outcomes.

Inclusion criteria

- Gestational age <32 0/7 weeks

- Included in Neonatal Research Network Generic Database

- Family has a telephone at home

- Anticipated availability for blood draw 4-6 weeks following 3rd vaccine dose

- Consent obtained before first dose of PCV-7 is given

Exclusion criteria

- Known immunodeficiency

- HIV exposure

- Parental non-consent

- Primary care pediatrician not willing to participate

- Enrollment in a conflicting trial

- Infant has not received first dose of PCV-7 vaccine by 3 months of age