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

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.