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Immunogenicity of Trivalent Influenza Vaccine in Extremely Low-birth-weight, Premature Versus Term Infants

D'Angio, Carl T. MD*; Heyne, Roy J. MD; Duara, Shahnaz MD; Holmes, Lucy C. MD§; O'Shea, T. Michael MD, MPH; Wang, Hongyue PhD**; Wang, Dongwen PhD**; Sánchez, Pablo J. MD; Welliver, Robert C. MD§; Ryan, Rita M. MD§; Schnabel, Kenneth C. MBA*∥; Hall, Caroline B. MDfor The Premature Infant Vaccine Collaborative

The Pediatric Infectious Disease Journal: July 2011 - Volume 30 - Issue 7 - p 570-574
doi: 10.1097/INF.0b013e31820c1fdf
Original Studies

Background: Influenza vaccine immunogenicity in premature infants is incompletely characterized.

Objective: To assess the immunogenicity of trivalent, inactivated influenza vaccine (TIV) in extremely low-birth-weight (≤1000 g birth weight) premature (<30 weeks gestation) infants. We hypothesized that geometric mean titers of influenza antibody would be lower in premature than in full-term (FT) (≥37 week) infants.

Design/Methods: In this prospective multicenter study, former premature and FT infants who were 6 to 17 months of age received 2 doses of TIV during the 2006–2007 or 2007–2008 influenza seasons. Sera were drawn before dose 1, and 4 to 6 weeks after dose 2. Antibody was measured by hemagglutination inhibition.

Results: Over 2 years, 41 premature and 42 FT infants were enrolled; 36 and 33 of these infants, respectively, had postvaccination titers available. Premature infants weighed less (mean, 1.3–1.8 kg difference) at the time of immunization than FT infants. Prevaccination titers did not differ between groups. Premature infants had higher postvaccination antibody geometric mean titers than FT infants to H1 (2006–2007, 1:513 vs. 1:91, P = 0.03; 2007–2008, 1:363 vs. 1:189, P = 0.02) and B/Victoria (2006–2007, 1:51 vs. 1:10, P = 0.02). More premature than FT infants had antibody titers ≥1:32 to B/Victoria (85% vs. 60%, P = 0.04) in 2007–2008. Two (5%) premature and 8 (19%) FT infants had adverse events, primarily fever, within 72 hours after vaccination. No child had medically diagnosed influenza.

Conclusions: Former premature infants had antibody responses to 2 TIV doses higher than or equal to those of FT children. Two TIV doses are immunogenic and well tolerated in extremely low-birth-weight, premature infants 6 to 17 months old.


From the *Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY; †Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX; ‡Department of Pediatrics, University of Miami, Miami, FL; §Department of Pediatrics, University at Buffalo School of Medicine, Buffalo, NY; ¶Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC; ∥Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY; and **Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY.

Accepted for publication December 17, 2010.

Supported in part by the Thrasher Research Fund and by the National Center for Research Resources grant (UL1 RR 024160).

This study was registered at (NCT00455169).

Address for correspondence: Carl T. D'Angio, MD, Division of Neonatology, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Box 651, 601 Elmwood Ave, Rochester, NY 14642. E-mail:

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© 2011 by Lippincott Williams & Wilkins, Inc.