MedImmune, LLC, Gaithersburg, Maryland, United States of America.
PLoS One. 2010 Oct 29;5(10):e13755. doi: 10.1371/journal.pone.0013755.
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.
ClinicalTrials.gov NCT00946101, NCT00945893.
单剂 2009 年 A/H1N1 型活流感减毒鼻内疫苗（LAIV）的安全性、耐受性和免疫原性已在儿童和成人中进行了评估。
方法/主要发现：两项随机、双盲、安慰剂对照研究在儿童（2-17 岁）和成人（18-49 岁）中完成。受试者以 4:1 的比例接受 2 剂 H1N1 LAIV 或安慰剂，间隔 28 天。主要安全性终点是首次给药后第 1-8 天体温≥38.3°C；主要免疫原性终点是经历剂量后血清反应的受试者比例。在每次给药后 14 天内记录症状和不良事件，并在最后一剂后 180 天内收集安全性数据。共有 326 名儿童（H1N1 LAIV，n=261；安慰剂，n=65）和 300 名成年人（H1N1 LAIV，n=240；安慰剂，n=60）入组。首次给药后，4 名（1.5%）儿童疫苗接种者和 1 名（1.5%）安慰剂接种者出现≥38.3°C的发热（发生率差异，0%；95%CI：-6.4%，3.1%）。没有成年人在第一次给药后出现发热。儿童（H1N1 LAIV 与安慰剂）的血清反应率分别为第 1 剂后 11.1%与 6.3%（发生率差异，4.8%；95%CI：-9.6%，13.8%）和第 2 剂后 32.0%与 14.5%（发生率差异，17.5%；95%CI：5.5%，27.1%）。成人的血清反应率分别为 6.1%与 0%（发生率差异，6.1%；95%CI：-5.6%，12.6%）和 14.9%与 5.6%（发生率差异，9.3%；95%CI：-0.8%，16.3%），分别在第 1 剂和第 2 剂后。首次给药后（H1N1 LAIV 与安慰剂）出现的症状在儿童中为 37.5%与 32.3%，在成人中为 41.7%与 31.7%。成人和儿童在第 2 剂后症状出现频率较低。没有与疫苗相关的严重不良事件发生。
结论/意义：在 2 至 49 岁的受试者中，两剂 H1N1 LAIV 的安全性和免疫原性与其他先前研究过的、有效的季节性三价 LAIV 制剂相似。
ClinicalTrials.gov NCT00946101，NCT00945893。
