Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2012;7(7):e41895. doi: 10.1371/journal.pone.0041895. Epub 2012 Jul 25.
H3N2 influenza viruses have now circulated in the human population for 43 years since the pandemic of 1968, accumulating sequence changes in the hemagglutinin (HA) and neuraminidase (NA) that are believed to be predominantly due to selection for escape from antibodies. Examination of mutations that persist and accumulate led to identification of antigenically significant mutations that are contained in five antigenic sites (A-E) mapped on to the H3 HA. In early H3N2 isolates, antigenic site A appeared to be dominant while in the 1990s site B seemed more important. To obtain experimental evidence for dominance of antigenic sites on modern H3 HAs, we have measured antibodies in plasma of human subjects who received the 2006-07 trivalent subunit influenza vaccine (H3 component A/Wisconsin/67/05) or the 2008-09 formulation (H3 component A/Uruguay/716/07). Plasmas were tested against expressed HA of Wisconsin-like influenza A/Oklahoma/309/06 and site-directed mutants in antigenic site A (NNES121-124ITEG, N126T, N133D, TSSS135-138GSNA, K140I, RSNNS142-146PGSG), and antigenic site B (HL156-157KS, KFK158-160GST, NDQI189-192QEQT, A196V). "Native ELISA" analysis and escape mutant selection with two human monoclonal antibodies demonstrated that antibody E05 binds to antigenic site A and 1_C02 binds to site B. We find that most individuals, after vaccination in seasons 2006-07 and/or 2008-09, showed dominance of antigenic site B recognition over antigenic site A. A minority showed dominance of site A in 2006 but these were reduced in 2008 when the vaccine virus had a site A mutation. A better understanding of immunodominance may allow prediction of future antigenic drift and assist in vaccine strain selection.
自 1968 年大流行以来，H3N2 流感病毒已在人群中传播了 43 年，其血凝素（HA）和神经氨酸酶（NA）发生了序列变化，这些变化被认为主要是由于逃避抗体选择的结果。对持续积累的突变进行检查，导致鉴定出包含在五个抗原位点（A-E）上的抗原性显著突变，这些突变映射到 H3 HA 上。在早期的 H3N2 分离株中，抗原位点 A 似乎占主导地位，而在 20 世纪 90 年代，抗原位点 B 似乎更为重要。为了获得现代 H3 HA 上抗原位点优势的实验证据，我们测量了接受 2006-07 年三价亚单位流感疫苗（H3 成分 A/Wisconsin/67/05）或 2008-09 年配方（H3 成分 A/Uruguay/716/07）的人类受试者血浆中的抗体。用表达的 A/Oklahoma/309/06 类似流感病毒的 HA 和抗原位点 A（NNES121-124ITEG、N126T、N133D、TSSS135-138GSNA、K140I、RSNNS142-146PGSG）和抗原位点 B（HL156-157KS、KFK158-160GST、NDQI189-192QEQT、A196V）的定点突变体对血浆进行了检测。“天然 ELISA”分析和用两种人源单克隆抗体进行逃逸突变体选择表明，抗体 E05 结合抗原位点 A，1_C02 结合抗原位点 B。我们发现，大多数人在 2006-07 年和/或 2008-09 年接种疫苗后，对抗原位点 B 的识别表现出优势，而对抗原位点 A 的识别则处于劣势。少数人在 2006 年表现出对位点 A 的优势，但当疫苗病毒发生位点 A 突变时，这种优势在 2008 年减少。更好地了解免疫优势可能有助于预测未来的抗原漂移，并有助于疫苗株的选择。
