Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials - PubMed (original) (raw)

Randomized Controlled Trial

Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials

Raburn M Mallory et al. PLoS One. 2010.

Abstract

Background: The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.

Methods/principal findings: Two 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/significance: In 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 registration: ClinicalTrials.gov NCT00946101, NCT00945893.

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Conflict of interest statement

Competing Interests: All authors have the following competing interests: 1) Financial: Paid employment by MedImmune, 2) Own stock or shares in MedImmune/AstraZeneca. This affiliation does not affect the authors' adherence to all PLoS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. Subject Disposition (ITT Population): (A) Children and (B) Adults.

ITT = intent to treat; LAIV = live attenuated influenza vaccine. *One child randomized to receive H1N1 LAIV was inadvertently administered placebo for dose 1; this subject also received placebo for dose 2. This subject was included in the H1N1 group for ITT analyses, but was grouped with placebo subjects for safety analyses.

Figure 2

Figure 2. Solicited Symptoms in (A) Children and (B) Adults Through Day 8 Postvaccination with Dose 1.

*P<0.05.

Figure 3

Figure 3. Solicited Symptoms in (A) Children and (B) Adults Through Day 8 Postvaccination with Dose 2.

*P<0.05.

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