Canadian Center for Vaccinology and the Departments of Pediatrics and Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
Pediatr Infect Dis J. 2012 Aug;31(8):848-58. doi: 10.1097/INF.0b013e31825e6cd6.
During the 2009-2010 influenza pandemic, we evaluated the immunogenicity and safety of different H1N1 2009 pandemic influenza vaccines delivering various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol oil-in-water emulsion-based adjuvant system) in children (NCT00976820).
Three hundred twenty-two healthy children 6 months to <9 years of age were randomized to receive 2 doses of nonadjuvanted (15 µg or 7.5 µg HA) or adjuvanted vaccine (3.75 µg HA/AS03A or 1.9 µg HA/AS03B), 21 days apart. Blood samples before and after each dose were tested for immune responses using hemagglutination inhibition and microneutralization assays. Safety assessments were done up to day 385.
The first dose of both AS03-adjuvanted vaccines elicited strong immune responses (seroprotection rates: 98.3%/99.0%; seroconversion rates: 94.9%/97.0%; geometric mean fold rises: 36.2/33.6), which were higher post-dose 2 (seroprotection rate: 100.0%/100%; seroconversion rate: 100.0%/98.8%; geometric mean fold rise: 157.1/151.6), meeting European regulatory criteria on days 21 and 42. The nonadjuvanted 15 µg HA vaccine also met the regulatory criteria after each dose; the 7.5 µg HA vaccine met them only post-dose 2. Six months post-dose 1, all vaccines except the nonadjuvanted 7.5 µg HA vaccine met European regulatory criteria. Neutralizing antibody response paralleled the hemagglutination inhibition immune response after each dose. Pain at the injection site, lasting 2-3 days, was more common following adjuvanted than nonadjuvanted vaccination.
AS03-adjuvanted H1N1 2009 pandemic influenza vaccine (3.75 µg or 1.9 µg HA), administered as 2 doses, was highly immunogenic, induced long-term immune response to 6 months, with a clinically acceptable safety profile in children aged 6 months to <9 years of age.
在 2009-2010 年流感大流行期间，我们评估了不同剂量的 H1N1 2009 流感大流行疫苗与或不与 AS03（一种基于生育酚油包水乳液的佐剂系统）联合免疫在儿童中的免疫原性和安全性（NCT00976820）。
322 名健康的 6 个月至<9 岁儿童随机接受 2 剂非佐剂（15 µg 或 7.5 µg HA）或佐剂疫苗（3.75 µg HA/AS03A 或 1.9 µg HA/AS03B），间隔 21 天。在每次剂量前后采血，使用血凝抑制和微量中和试验检测免疫反应。安全性评估至第 385 天。
两种 AS03 佐剂疫苗的第一剂均能引起强烈的免疫反应（血清保护率：98.3%/99.0%；血清转化率：94.9%/97.0%；几何平均倍数升高：36.2/33.6），第二剂后更高（血清保护率：100.0%/100.0%；血清转化率：100.0%/98.8%；几何平均倍数升高：157.1/151.6），符合欧洲监管标准第 21 天和第 42 天。非佐剂 15 µg HA 疫苗在每次剂量后也符合监管标准；7.5 µg HA 疫苗仅在第二剂后符合。第一剂后 6 个月，除非佐剂 7.5 µg HA 疫苗外，所有疫苗均符合欧洲监管标准。每次剂量后，中和抗体反应与血凝抑制免疫反应平行。与非佐剂疫苗相比，接种佐剂疫苗后更常见注射部位疼痛，持续 2-3 天。
作为 2 剂接种，AS03 佐剂 H1N1 2009 流感大流行疫苗（3.75 µg 或 1.9 µg HA）具有高度免疫原性，可诱导 6 个月的长期免疫反应，在 6 个月至<9 岁儿童中具有可接受的临床安全性。
