Efficacy and Safety of 1 and 2 Doses of Live Attenuated Influenza Vaccine in Vaccine-Naive Children

Background: We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to <36 months. Patients/Methods: Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAW recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAW received saline placebo and 1 block who were randomized to placebo received LAIV. Results: In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAW was 73.5% and 57.7%, respectively, against anti-genically similar strains. In year 2, absolute efficacy of a single dose of LAW was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAW in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAW in year 1 and placebo in year 2. Safety and tolerability of LAW were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAW group in year 1 and in both LAW groups versus placebo in years 1 and 2. Conclusions: One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAW excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAW in children >= 2 years of age.