Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response A Randomized Clinical Trial
Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response A Randomized Clinical Trial
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DOI：
10.1001/jama.2015.7916
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发表时间：
2015-07-21
影响因子：
120.7
通讯作者：
Bellamy, Abbie R.
中科院分区：
文献类型：
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作者：
Jackson, Lisa A.;Campbell, James D.;Bellamy, Abbie R.
中国于2013年首次报告人感染甲型H7N9禽流感病毒，并继续发生。血凝素H7单独给药是一种不良的免疫原，需要评估有佐剂的H7N9疫苗。目的评估有和没有AS 03佐剂的灭活H7N9疫苗的免疫原性和安全性，以及包括顺序给药含AS 03和MF 59的制剂以及有佐剂和无佐剂制剂的混合疫苗方案。2013年9月至2013年11月，在5家美国研究中心进行的II期试验入组了980名19至64岁的成人;安全性随访于2015年1月完成。干预H7N9疫苗在第0天和第21天以3.75 μ g、7.5 μ g、15 μ g和45 μ g血凝素，有或没有AS 03或MF 59佐剂现场混合。主要结果和指标：第二次接种后21天血凝抑制抗体（HIA）滴度达到40或更高的比例;第一次接种后12个月内疫苗相关严重不良事件;接种后7天内征集的体征和症状。在给予2剂含有15 μ g血凝素的H7N9制剂（不含佐剂、含AS 03佐剂或含MF 59佐剂）后，达到40或更高HIA滴度的比例为2%（95% CI，0%-7%）无佐剂（n = 94），84%使用AS 03佐剂（n = 96）时为57%（95%CI，76%-91%），使用MF 59佐剂（n = 92）时为57%（95%CI，47%-68%）（对于AS 03和MF 59方案的比较，P < .001）。交替使用AS 03和MF 59佐剂制剂的2种方案导致AS 03和MF 59佐剂制剂的几何平均滴度（GMT）较低。（41.5 [95% CI，31.7-54.4]; n = 92）和（58.6 [95%CI，44.3-77.6]; n = 96）比由2种AS 03佐剂制剂诱导的组（n = 96）（103.4 [95%CI，78.7-135.9]; P
IMPORTANCE Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continue to occur. Hemagglutinin H7 administered alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines.OBJECTIVE To evaluate the immunogenicity and safety of an inactivated H7N9 vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that included sequential administration of AS03- and MF59-containing formulations and of adjuvanted and unadjuvanted formulations.DESIGN, SETTING, AND PARTICIPANTS Double-blind, phase 2 trial at 5 US sites enrolled 980 adults aged 19 through 64 years from September 2013 through November 2013; safety follow-up was completed in January 2015.INTERVENTIONS The H7N9 vaccine was given on days 0 and 21 at nominal doses of 3.75 mu g, 7.5 mu g, 15 mu g, and 45 mu g of hemagglutinin with or without AS03 or MF59 adjuvant mixed on site. MAIN OUTCOMES AND MEASURES Proportions achieving a hemagglutination inhibition antibody (HIA) titer of 40 or higher at 21 days after the second vaccination; vaccine-related serious adverse events through 12 months after the first vaccination; and solicited signs and symptoms after vaccination through day 7.RESULTS Two doses of vaccine were required to induce detectable antibody titers in most participants. After 2 doses of an H7N9 formulation containing 15 mu g of hemagglutinin given without adjuvant, with AS03 adjuvant, or with MF59 adjuvant, the proportion achieving an HIA titer of 40 or higher was 2%(95% CI, 0%-7%) without adjuvant (n = 94), 84%(95% CI, 76%-91%) with AS03 adjuvant (n = 96), and 57%(95% CI, 47%-68%) with MF59 adjuvant (n = 92) (P < .001 for comparison of the AS03 and MF59 schedules). The 2 schedules alternating AS03- and MF59-adjuvanted formulations led to lower geometric mean titers (GMTs) of (41.5 [95% CI, 31.7-54.4]; n = 92) and (58.6 [95% CI, 44.3-77.6]; n = 96) than the group induced by 2 AS03-adjuvanted formulations (n = 96) (103.4 [95% CI, 78.7-135.9]; P