Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability.
Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability.
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DOI：
10.1186/1472-6750-12-77
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发表时间：
2012-10-30
影响因子：
3.5
通讯作者：
Cox MM
中科院分区：
文献类型：
--
作者：
Feshchenko E;Rhodes DG;Felberbaum R;McPherson C;Rininger JA;Post P;Cox MM
最近发生的甲型H1N1流感疫情就说明了疫苗生产工艺的缺陷。 A/California/07/2009 H1N1 大流行性流感疫苗或 A(H1N1)pdm09 由于产量低和抗原稳定性差导致生产延迟，因此供货较晚且供应短缺。重组技术提供了缩短制造时间的机会。使用杆状病毒表达载体系统（BEVS）生产的季节性流感三价重组血凝素（rHA）候选疫苗在人体临床研究中被证明与鸡蛋来源的三价灭活疫苗（TIV）一样有效和安全。在这项研究中，我们描述了 A/California/07/2009 rHA 蛋白的特征，并将 H1N1 大流行性 rHA 与其他季节性 rHA 蛋白进行了比较。我们的数据表明，与其他 rHA 蛋白一样，纯化的 A/California/07/2009 rHA 形成 20-40 nm 的多聚玫瑰花状颗粒，通过血凝抑制 (HAI) 抗体滴度测定，这些颗粒在小鼠中具有生物活性和免疫原性。然而，蛋白水解消化分析显示，A/California/07/2009 rHA 比源自其他季节性流感病毒的 rHA 蛋白更容易被蛋白水解降解。我们鉴定了多种血凝素 (HA) 蛋白中保守的特定蛋白水解位点，该位点在 A/California/07/2009 HA 中可能更容易接近，可能是由于其蛋白结构的差异所致，并且可能导致抗原稳定性较低。我们的结论是，与重组季节性流感疫苗类似，重组 A(H1N1)pdm09 疫苗的性能可能与许可的 A(H1N1)pdm09 疫苗相当，并且可以提供制造优势。
The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins. Our data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability. We conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages.
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影响因子：
5.5
作者：
Wang K;Holtz KM;Anderson K;Chubet R;Mahmoud W;Cox MM
通讯作者：
Cox MM
影响因子：
3.7
作者：
Kistner O;Crowe BA;Wodal W;Kerschbaum A;Savidis-Dacho H;Sabarth N;Falkner FG;Mayerhofer I;Mundt W;Reiter M;Grillberger L;Tauer C;Graninger M;Sachslehner A;Schwendinger M;Brühl P;Kreil TR;Ehrlich HJ;Barrett PN
通讯作者：
Barrett PN
影响因子：
4.4
作者：
Cox MM;Patriarca PA;Treanor J
通讯作者：
Treanor J
影响因子：
5.5
作者：
Gordon DL;Sajkov D;Woodman RJ;Honda-Okubo Y;Cox MM;Heinzel S;Petrovsky N
通讯作者：
Petrovsky N
影响因子：
5.5
作者：
Treanor, John J.;El Sahly, Hana;Cox, Manon
通讯作者：
Cox, Manon