Immunogenicity of PCV-7 Vaccine in VLBW Infants

Completed

• Conditions: Streptococcus Pneumoniae; Infant, Small for Gestational Age; Pneumococcal Infections; Infant, Newborn; Infant, Premature; Infant, Low Birth Weight

• Registration Number: NCT00273325
• Lead Sponsor: NICHD Neonatal Research Network

Brief Summary

Premature infants are at a high risk for pneumonia. The PCV-7 vaccine effectively prevents the invasive disease from Streptococcus pneumoniae in full-term infants, but was not thoroughly studied in premature infants. This study evaluated the effectiveness and safety of the vaccine given in routine practice to very low birth weight infants, looking at blood antibody levels 4-6 weeks after the final vaccine dose, and adverse events, survival, infections, and neurodevelopmental outcomes at 18-22 months corrected age.

Detailed Description

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.

Study Timeline

• Study Start: 2004-07
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2006-01-05
• Study First Posted: 2006-01-09
• Primary Completion: 2007-07
• Study Completion: 2009-03
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-20
• Last Update Posted: 2019-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 368

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml	4-6 weeks following the third dose of PCV-7

Secondary Outcome Measures

Name	Time	Method
Pneumococcal capsular polysaccharide antibody >=0.15 μg/ml for the other six vaccine serotypes	4-6 weeks following the third dose of PCV-7
Opsonization of 6B pneumococcal capsular polysaccharide plus 1 low immunogenicity, high prevalence serotype (e.g., 23F) among infants in the lowest quartile of antibody response	4-6 weeks following the third dose of PCV-7
Levels of antibody >=0.15 μg/ml and >=1.0 μg/ml to Hib polyribosylribitol	4-6 weeks following the third dose of PCV-7
Pneumococcal capsular polysaccharide antibodies >=1.0 μg/ml for all seven vaccine serotypes	4-6 weeks following the third dose of PCV-7
Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes	4-6 weeks following the third dose of PCV-7
Pneumococcal capsular polysaccharide antibodies >=0.15 μg/ml and >=1.0 μg/ml, and geometric mean titers of antibody, to the seven vaccine serotypes in children completing the primary series, regardless of postnatal age	4-6 weeks following the third dose of PCV-7
Effect of pneumococcal conjugate immunization status (complete & timely v. complete v. incomplete) on outcome (survival, serious infection, neurodevelopmental outcome) at 18-22 months corrected age in infants <=1000g	18-22 months corrected age
Effect of possible mediating variables on the achievement of levels of serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml	4-6 weeks following the third dose of PCV-7
Avidity of antibody to Hib-PRP among infants in the lowest quartile of antibody response,regardless of postnatal or gestational age	4-6 weeks following the third dose of PCV-7

Trial Locations

Locations (10)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Wake Forest University; 🇺🇸 Charlotte, North Carolina, United States

RTI International; 🇺🇸 Durham, North Carolina, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Texas Southwestern Medical Center at Dallas; 🇺🇸 Dallas, Texas, United States