Immunogenicity of PCV-7 Vaccine in VLBW Infants (PCV-7)

• ClinicalTrials.gov Identifier: NCT00273325
• Recruitment Status: Completed
• First Posted: January 9, 2006
• Last Update Posted: March 22, 2019
• Sponsor: NICHD Neonatal Research Network
• Collaborators: National Center for Research Resources (NCRR); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): NICHD Neonatal Research Network

Study Description

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.

Condition or disease
Pneumococcal Infections; Streptococcus Pneumoniae; Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature

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 Design

• Study Type: Observational
• Actual Enrollment: 368 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Observational Study of the Immunogenicity of Heptavalent Pneumococcal Conjugate Vaccine in Very-low-birth-weight Infants
• Study Start Date: July 2004
• Actual Primary Completion Date: July 2007
• Actual Study Completion Date: March 2009

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]

Secondary Outcome Measures :

1. Pneumococcal capsular polysaccharide antibody >=0.15 μg/ml for the other six vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
2. Pneumococcal capsular polysaccharide antibodies >=1.0 μg/ml for all seven vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
3. Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
4. 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 [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
5. 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 [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
6. Effect of possible mediating variables on the achievement of levels of serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
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 [ Time Frame: 18-22 months corrected age ]
8. Levels of antibody >=0.15 μg/ml and >=1.0 μg/ml to Hib polyribosylribitol [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]
9. Avidity of antibody to Hib-PRP among infants in the lowest quartile of antibody response,regardless of postnatal or gestational age [ Time Frame: 4-6 weeks following the third dose of PCV-7 ]

Biospecimen Retention:   Samples With DNA

Serum was separated from blood samples. After all study assays were completed on all subjects, if a subject's parents asked that his/her serum not be stored, the serum was destroyed. For subjects whose parents permit it, leftover serum was re-labeled with a new, randomly-generated unique de-identifier, linked only to the subject's gestational age, birth weight, and chronologic age at the time of sampling. The link to any other subject identifiers will then be destroyed. The serum will be stored indefinitely at the University of Rochester for other, non-genetic-testing-related research.

Eligibility Criteria

• Ages Eligible for Study: up to 3 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Infants <1,500g birth weight who receive the 3-dose primary series of PCV-7 immunization by 3 months and complete it by 8 months postnatal age

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, California

Stanford University

Palo Alto, California, United States, 94304

United States, Florida

University of Miami

Miami, Florida, United States, 33136

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30303

United States, Michigan

Wayne State University

Detroit, Michigan, United States, 48201

United States, New York

University of Rochester

Rochester, New York, United States, 14642

United States, North Carolina

Wake Forest University

Charlotte, North Carolina, United States, 27157

RTI International

Durham, North Carolina, United States, 27705

Duke University

Durham, North Carolina, United States, 27710

United States, Texas

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States, 75235

Sponsors and Collaborators

NICHD Neonatal Research Network

National Center for Research Resources (NCRR)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Ronald N. Goldberg, MD; Duke University
• Principal Investigator: Barbara J. Stoll, MD; Emory University
• Principal Investigator: Abhik Das, PhD; RTI International
• Principal Investigator: Krisa P. Van Meurs, MD; Stanford University
• Principal Investigator: Waldemar A. Carlo, MD; University of Alabama at Birmingham
• Principal Investigator: Shahnaz Duara, MD; University of Miami
• Principal Investigator: Carl T. D'Angio, MD; University of Rochester
• Principal Investigator: Pablo J. Sanchez, MD; University of Texas, Southwestern Medical Center at Dallas
• Principal Investigator: T. Michael O'Shea, MD MPH; Wake Forest University
• Principal Investigator: Seetha Shankaran, MD; Wayne State University

More Information

Additional Information:

NICHD Neonatal Research Network 

Publications of Results:

D'Angio CT, Heyne RJ, O'Shea TM, Schelonka RL, Shankaran S, Duara S, Goldberg RN, Stoll BJ, Van Meurs KP, Vohr BR, Das A, Li L, Burton RL, Hastings B, Phelps DL, Sanchez PJ, Carlo WA, Stevenson DK, Higgins RD; NICHD Neonatal Research Network. Heptavalent pneumococcal conjugate vaccine immunogenicity in very-low-birth-weight, premature infants. Pediatr Infect Dis J. 2010 Jul;29(7):600-6. doi: 10.1097/INF.0b013e3181d264a6.

Wynn JL, Li L, Cotten CM, Phelps DL, Shankaran S, Goldberg RN, Carlo WA, Van Meurs K, Das A, Vohr BR, Higgins RD, Stoll BJ, D'Angio CT. Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants. J Perinatol. 2013 Aug;33(8):613-8. doi: 10.1038/jp.2013.5. Epub 2013 Jan 31.

Ang JY, Lua JL, Asmar BI, Shankaran S, Heyne RJ, Schelonka RL, Das A, Li L, Jackson DM, Higgins RD, D'Angio CT; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Nasopharyngeal carriage of Streptococcus pneumoniae in very low-birth-weight infants after administration of heptavalent pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med. 2010 Dec;164(12):1173-5. doi: 10.1001/archpediatrics.2010.233. No abstract available.

D'Angio CT, Murray TE, Li L, Heyne RJ, O'Shea TM, Schelonka RL, Shankaran S, Duara S, Goldberg RN, Stoll BJ, Stevenson DK, Vohr BR, Phelps DL, Carlo WA, Pichichero ME, Das A, Higgins RD; NICHD Neonatal Research Network. Immunogenicity of Haemophilus influenzae type b protein conjugate vaccines in very low birth weight infants. Pediatr Infect Dis J. 2013 Dec;32(12):1400-2. doi: 10.1097/01.inf.0000437263.04493.7c. No abstract available.

• Responsible Party: NICHD Neonatal Research Network
• ClinicalTrials.gov Identifier: NCT00273325
• Other Study ID Numbers: NICHD-NRN-0031; UL1RR024128 ( U.S. NIH Grant/Contract ); UL1RR024160 ( U.S. NIH Grant/Contract ); UL1RR024982 ( U.S. NIH Grant/Contract ); UL1RR025008 ( U.S. NIH Grant/Contract ); UL1RR025744 ( U.S. NIH Grant/Contract ); UL1RR025777 ( U.S. NIH Grant/Contract ); M01RR016587 ( U.S. NIH Grant/Contract ); M01RR000030 ( U.S. NIH Grant/Contract ); M01RR000032 ( U.S. NIH Grant/Contract ); M01RR000039 ( U.S. NIH Grant/Contract ); M01RR000044 ( U.S. NIH Grant/Contract ); M01RR000633 ( U.S. NIH Grant/Contract ); M01RR000070 ( U.S. NIH Grant/Contract ); M01RR007122 ( U.S. NIH Grant/Contract ); U01HD036790 ( U.S. NIH Grant/Contract ); U10HD021385 ( U.S. NIH Grant/Contract ); U10HD021397 ( U.S. NIH Grant/Contract ); U10HD027851 ( U.S. NIH Grant/Contract ); U10HD027880 ( U.S. NIH Grant/Contract ); U10HD034216 ( U.S. NIH Grant/Contract ); U10HD040492 ( U.S. NIH Grant/Contract ); U10HD040498 ( U.S. NIH Grant/Contract ); U10HD040521 ( U.S. NIH Grant/Contract ); U10HD040689 ( U.S. NIH Grant/Contract )
• First Posted: January 9, 2006
• Last Update Posted: March 22, 2019
• Last Verified: March 2019

Keywords provided by NICHD Neonatal Research Network:

NICHD Neonatal Research Network; Very Low Birth Weight (VLBW); Extremely Low Birth Weight (ELBW); Prematurity; Pneumococcal Vaccines; Vaccines, Conjugate; Immunogenicity; Vaccine Response; Heptavalent pneumococcal conjugate vaccine (PCV-7); pneumococcal polysaccharide, type 6B; Pneumococcal polysaccharide, type 14; Pneumococcal polysaccharide, type 19F,; Pneumococcal polysaccharide, 23F; Pneumococcal polysaccharide, 18C; Pneumococcal polysaccharide, 4; Pneumococcal polysaccharide, 9V

Additional relevant MeSH terms:

Pneumonia, Pneumococcal; Pneumococcal Infections; Birth Weight; Body Weight; Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia, Bacterial