A chimeric influenza hemagglutinin delivered by parainfluenza virus 5 vector induces broadly protective immunity against genetically divergent influenza a H1 viruses in swine.
A chimeric influenza hemagglutinin delivered by parainfluenza virus 5 vector induces broadly protective immunity against genetically divergent influenza a H1 viruses in swine.
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DOI：
10.1016/j.vetmic.2020.108859
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发表时间：
2020-11
影响因子：
3.3
通讯作者：
Huber VC
中科院分区：
文献类型：
--
作者：
Li Z;Zaiser SA;Shang P;Heiden DL;Hajovsky H;Katwal P;DeVries B;Baker J;Richt JA;Li Y;He B;Fang Y;Huber VC
当重组抗原由PIV 5（PIV 5 -113）表达时，通过DNA改组（HA-113）产生的基于HA的候选疫苗可能具有免疫原性。由PIV 5 -113疫苗诱导的免疫力可保护小鼠免受用于产生疫苗的5种亲本HA中的4种的感染。由PIV 5 -113诱导的免疫力可保护猪免受已知在猪中具有传染性的流感病毒分离株的感染。猪是人类流感病毒的重要宿主，流感给养猪业造成重大经济损失。正如2009年H1N1流感大流行期间所证明的，控制猪流感病毒感染是阻止人流感病毒出现的关键一步。迫切需要一种有效的疫苗，可以诱导针对异源流感病毒株的广泛保护性免疫。在我们以前的研究中[McCormick等人，二〇一五年; PLoS One，10（6）：e0127649]，我们使用分子育种（DNA改组）策略来增加在单个甲型流感病毒嵌合血凝素（HA）蛋白内表达的可变和保守表位的宽度。嵌合HA使用来自2009年大流行病毒和具有人畜共患传播史的猪流感病毒的亲本HA构建。在目前的研究中，我们使用副流感病毒5（PIV-5）作为载体表达这些嵌合HA抗原之一，HA-113。拯救了表达HA-113的重组PIV-5（PIV 5 -113），并在小鼠和猪模型中检测了免疫原性和保护效力。结果表明，PIV 5 -113可以保护小鼠和猪免受表达亲本HA的病毒的攻击。针对其他基因多样化的流感H1表达病毒的保护性免疫力得到了扩展。我们的工作表明，基于PIV 5的流感疫苗作为猪疫苗是有效的。在通用流感疫苗的开发和PIV 5 -113作为候选通用疫苗的潜在贡献的背景下，讨论了PIV 5疫苗载体和嵌合HA-113抗原。
An HA-based vaccine candidate, created by DNA shuffling (HA-113), can be immunogenic when recombinant antigen is expressed by PIV5 (PIV5-113). Immunity induced by the PIV5-113 vaccine can protect mice against infection with 4 of 5 parental HAs used to create the vaccine. Immunity induced by PIV5-113 can protect pigs against infection with an influenza virus isolate that is known to be infectious in pigs. Pigs are an important reservoir for human influenza viruses, and influenza causes significant economic loss to the swine industry. As demonstrated during the 2009 H1N1 pandemic, control of swine influenza virus infection is a critical step toward blocking emergence of human influenza virus. An effective vaccine that can induce broadly protective immunity against heterologous influenza virus strains is critically needed. In our previous studies [McCormick et al., 2015; PLoS One, 10(6):e0127649], we used molecular breeding (DNA shuffling) strategies to increase the breadth of the variable and conserved epitopes expressed within a single influenza A virus chimeric hemagglutinin (HA) protein. Chimeric HAs were constructed using parental HAs from the 2009 pandemic virus and swine influenza viruses that had a history of zoonotic transmission to humans. In the current study, we used parainfluenza virus 5 (PIV-5) as a vector to express one of these chimeric HA antigens, HA-113. Recombinant PIV-5 expressing HA-113 (PIV5-113) were rescued, and immunogenicity and protective efficacy were tested in both mouse and pig models. The results showed that PIV5-113 can protect mice and pigs against challenge with viruses expressing parental HAs. The protective immunity was extended against other genetically diversified influenza H1-expressing viruses. Our work demonstrates that PIV5-based influenza vaccines are efficacious as vaccines for pigs. The PIV5 vaccine vector and chimeric HA-113 antigen are discussed in the context of the development of universal influenza vaccines and the potential contribution of PIV5-113 as a candidate universal vaccine.
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影响因子：
19
作者：
Freidl, G. S.;Meijer, A.;Koopmans, M.
通讯作者：
Koopmans, M.
DOI：
10.1177/2051013615595595
发表时间：
2015-07-01
期刊：
Therapeutic advances in vaccines
影响因子：
--
作者：
Cox, Manon M J;Izikson, Ruvim;Dunkle, Lisa
通讯作者：
Dunkle, Lisa
影响因子：
33.7
作者：
Grohskopf, Lisa A.;Sokolow, Leslie Z.;Bresee, Joseph S.
通讯作者：
Bresee, Joseph S.
影响因子：
3.7
作者：
Chen, Zhenhai;Xu, Pei;He, Biao
通讯作者：
He, Biao
影响因子：
4.4
作者：
Anderson, Tavis K.;Nelson, Martha I.;Vincent, Amy L.
通讯作者：
Vincent, Amy L.