Efficacy Studies of Influenza Vaccines: Effect of End Points Used and Characteristics of Vaccine Failures
Efficacy Studies of Influenza Vaccines: Effect of End Points Used and Characteristics of Vaccine Failures
复制标题
DOI：
10.1093/infdis/jir015
复制
发表时间：
2011-05-01
影响因子：
6.4
通讯作者：
Monto, Arnold S.
中科院分区：
文献类型：
--
作者：
Petrie, Joshua G.;Ohmit, Suzanne E.;Monto, Arnold S.
方法.我们比较了一项为期3年的灭活疫苗和减毒活疫苗安慰剂对照试验中甲型H3N2流感和B流感病例的特征，并评估了用于确定疗效的实验室终点。尽管疾病持续时间和报告的症状在干预措施中没有差异，但灭活疫苗组的流感受试者报告医疗护理疾病的可能性低于安慰剂组。还通过实时聚合酶链反应（rtPCR）鉴定了在细胞培养中分离的所有甲型（H3 N2）和B型流感病例。然而，只有69%的通过rtPCR鉴定的A型（H3N2）病例也是在细胞培养中分离的。在减毒活疫苗失败的病例中，分离频率最低，反映了较低的标本病毒载量。在rtPCR鉴定的甲型H3N2流感病例中，90%的安慰剂和87%的减毒活疫苗接种者，但只有23%的灭活疫苗接种者表现出感染的血清学确认。在流感疫苗有效性研究中，使用rtPCR进行病毒鉴定是理想的终点。细胞培养中的分离会遗漏病例，单独的血清学终点会高估灭活疫苗的效力。
Methods. We compared characteristics of influenza A (H3N2) and B cases from 3 years of a comparative placebo-controlled trial of inactivated and live attenuated vaccines, and we evaluated the laboratory end points used to determine efficacy.Results. Although illness duration and reported symptoms did not differ by intervention, subjects with influenza in the inactivated vaccine group were less likely than those in the placebo group to report medically attended illnesses. All influenza type A (H3N2) and B cases isolated in cell culture were also identified by real-time polymerase chain reaction (rtPCR). However, only 69% of type A (H3N2) cases identified by rtPCR also were isolated in cell culture. Isolation frequency was lowest among live attenuated vaccine failures, a reflection of lower specimen viral loads. Among cases of rtPCR identified influenza A (H3N2), 90% of placebo and 87% of live attenuated vaccine recipients but only 23% of inactivated vaccine recipients demonstrated serologic confirmation of infection.Conclusions. In influenza vaccine efficacy studies, virus identification using rtPCR is the ideal end point. Isolation in cell culture will miss cases, and a serologic end point alone will overestimate inactivated vaccine efficacy.