A Randomized Trial
Terry Nolan, MBBS, PhD; Jodie McVernon, MBBS, PhD; Maryanne Skeljo, PhD; Peter Richmond, MBBS; Ushma Wadia, MBBS; Stephen Lambert, MBBS, MAppEpid; Michael Nissen, BMedSc, MBBS; Helen Marshall, MBBS, MPH; Robert Booy, MD, MSc; Leon Heron, MBChB, MPH; Gunter Hartel, MS, PhD; Michael Lai, MBBS, MMedSc; Russell Basser, MBBS, MD; Charmaine Gittleson, MBBCh; Michael Greenberg, MD, MPH
JAMA. 2010;303(1):(doi:10.1001/jama.2009.1911).
Context In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children.
Objective To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children.
Design, Setting, and Participants Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia.
Intervention Intramuscular injection of 15 µg or 30 µg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart.
Main Outcome Measures Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination.
Results Following the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-µg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-µg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI, 11.8-15.6) and 18.3 (95% CI, 15.7-21.4). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity.
Conclusion One 15-µg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity.
Trial Registration clinicaltrials.gov Identifier: NCT00940108
Author Affiliations: Vaccine and Immunization Research Group, School of Population Health, University of Melbourne, and Murdoch Children’s Research Institute, Victoria, Australia (Drs Nolan, McVernon, and Skeljo); School of Pediatrics and Child Health, University of Western Australia, and Telethon Institute for Child Health Research, Subiaco, Western Australia (Drs Richmond and Wadia); Queensland Pediatric Infectious Diseases Laboratory, Royal Children’s Hospital, Herston, Queensland, Australia (Drs Lambert and Nissen); Department of Pediatrics, University of Adelaide, and Women’s and Children’s Hospital, North Adelaide, South Australia (Dr Marshall); National Center for Immunization Research and Surveillance of Vaccine Preventable Diseases, University of Sydney, and Children’s Hospital at Westmead, New South Wales, Australia (Drs Booy and Heron); and Clinical Research and Development, CSL Limited, Parkville, Victoria, Australia (Drs Hartel, Lai, Basser, Gittleson, and Greenberg).
