Safety and Immunogenicity Following Administration of a Live, Attenuated Monovalent 2009 H1N1 Influenza Vaccine to Children and Adults in Two Randomized Controlled Trials

Abstract

BackgroundThe safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.Methods/Principal FindingsTwo randomized, double-blind, placebo-controlled studies were completed in children (2–17 y) and adults (18–49 y). Subjects were assigned 4∶1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1–8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: –6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: –9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: –5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: –0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred.Conclusions/SignificanceIn subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV.Trial RegistrationClinicalTrials.gov NCT00946101, NCT00945893

Safety, immunogenicity and infectivity of new live attenuated influenza vaccines

“…This provided an opportunity to assess not only the vaccines' immunogenicity, but also their clinical efficacy. Both LAIVs were tested in randomized, placebocontrolled trials in adults and children shortly after the pandemic was declared [56,57]. As expected, the vaccines were found to be safe and well tolerated by both age groups.…”

Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit

“…The published AE rates vary greatly (0.2---41.7% of all vaccinated individuals), depending particularly on the study population and on the vigilance system involved. 171,172 The incidence density varies between 9 and 31.8 AEs for every 100,000 administered doses. Problems in this sense are more frequent in the first 24 h after vaccination in the younger population, and there are no gender differences.…”

Quadrivalent Ann Arbor strain live-attenuated influenza vaccine

“…Functional serum antibody titers as measured by HAI are generally regarded as a correlate of protection for inactivated influenza vaccines. However, studies have demonstrated that LAIV can induce protection from influenza illness in the absence of robust serum antibody responses, as measured by fourfold rises in HAI [42][43][44][45]. Mucosal [46] and cell-mediated immune responses [47] are important contributors to LAIV-induced immunity; however, these responses are difficult to measure, and there are no standard or widely accepted assays.…”