Durviaux Serge, Treanor John, Beran Jiri, Duval Xavier, Esen Meral, Feldman Gregory, Frey Sharon E, Launay Odile, Leroux-Roels Geert, McElhaney Janet E, Nowakowski Andrzej, Ruiz-Palacios Guillermo M, van Essen Gerrit A, Oostvogels Lidia, Devaster Jeanne-Marie, Walravens Karl
GlaxoSmithKline Vaccines, Rixensart, Belgium.
Clin Vaccine Immunol. 2014 Mar;21(3):271-9. doi: 10.1128/CVI.00544-13. Epub 2013 Dec 26.
Estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. This study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (HA) gene-encoded HA1 domain is a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza virus vaccine efficacy trial involving >43,000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380 viruses), A(H1N1) (29 viruses), B(Yamagata) (23 viruses), and B(Victoria) (66 viruses) from 603 PCR- or culture-confirmed specimens. Unlike the B strains, most A(H3N2) (377 viruses) and all A(H1N1) viruses were classified as homologous to the respective vaccine strains based on their HA1 domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48% (182/380) of A(H3N2) and 86% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses classified as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR is a sensitive diagnostic method for confirming influenza virus cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity; hence, it may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine strain for estimating vaccine efficacy in a prospective clinical trial.
针对季节性流感病毒疫苗有效性的评估，是通过将临床突破性病例中分离出的流感病毒与疫苗中所含毒株的抗原性进行比较来指导的。本研究检验了使用血凝素（HA）基因编码的HA1结构域的序列分析来预测抗原性，是否是一种比使用传统血凝抑制（HI）试验更简便的替代方法，传统HI试验需要培养流感病毒。样本取自2008 - 2009季节一项涉及超过43000名参与者的三价流感病毒疫苗效力试验中出现的突破性病例。从603份经PCR或培养确认的样本中，总共成功鉴定出498株流感病毒，分别为A(H3N2)（380株病毒）、A(H1N1)（29株病毒）、B(Yamagata)（23株病毒）和B(Victoria)（66株病毒）。与B型毒株不同，大多数A(H3N2)（377株病毒）和所有A(H1N1)病毒，根据其HA1结构域核酸序列，被归类为与各自的疫苗毒株同源。对48%（182/380）的A(H3N2)病毒和86%（25/29）的A(H1N1)病毒测定了相对于各自疫苗毒株的HI滴度以及PCR分型。通过序列分析归类为同源的A(H3N2)和A(H1N1)病毒中，84%通过HI检测与各自的疫苗毒株匹配。然而，这些同源的A(H3N2)和A(H1N1)病毒显示出广泛的相对HI滴度范围。因此，尽管PCR是确认流感病毒病例的一种灵敏诊断方法，但HA1序列分析在准确预测抗原性方面似乎价值有限；因此，在一项前瞻性临床试验中，将临床样本归类为与疫苗毒株同源或异源以评估疫苗效力可能并不合适。
