Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge.
Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge.
复制标题
DOI：
10.1016/j.vaccine.2021.02.077
复制
发表时间：
2021-04-01
期刊：
影响因子：
5.5
通讯作者：
Ma W
中科院分区：
文献类型：
--
作者：
Lee J;Li Y;Li Y;Cino-Ozuna AG;Duff M;Lang Y;Ma J;Sunwoo S;Richt JA;Ma W
猪流感是养猪业的一种重要疾病。目前使用的全灭活病毒（WIV）疫苗，当疫苗株与感染的病毒不匹配时，可在猪中诱导疫苗相关增强型呼吸道疾病（VAERD）。减毒流感病毒活疫苗（LAIV）可有效保护猪免受同源和异源猪流感病毒感染，而不会诱导VAERD，但由于与循环病毒的潜在重配，存在安全性问题。本文中，我们使用嵌合蝙蝠流感病毒Bat 09：mH 3 mN 2，其含有A/swine/Texas/4199-2/1998（H3 N2）的表面HA和NA基因开放阅读框以及来自新型蝙蝠H17 N10病毒的六个内部基因，以开发修饰的减毒活病毒（MLV）作为疫苗候选物，其不能通过共感染与典型的甲型流感病毒重新配型。生成了两种减毒MLV候选疫苗，包括表达截短型NS 1（Bat 09：mH 3 mN 2-NS 1 -128，MLV 1）或同时表达截短型NS 1和猪IL-18（Bat 09：mH 3 mN 2-NS 1 -128-IL-18，MLV 2）的病毒，并使用WIV疫苗作为对照，在猪中评价了其抗异源H3 N2病毒的能力。与WIV疫苗相比，两种MLV疫苗均能够减少肺部病变和病毒复制，并限制鼻内病毒脱落（无VAERD），还诱导了肺粘膜伊加应答水平显著升高，并显著增加了针对攻毒病毒的抗原特异性IFN-γ分泌细胞数量。然而，在MLV 1和MLV 2之间未观察到有效性的显著差异。这些结果表明，蝙蝠流感病毒载体MLV疫苗可用作预防猪流感的安全活疫苗。
Swine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199-2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccine as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza.
登录
查看更多内容
影响因子：
5.5
作者：
Masic, Aleksandar;Lu, Xinya;Zhou, Yan
通讯作者：
Zhou, Yan
影响因子：
5.4
作者：
Denton, Alice E.;Doherty, Peter C.;La Gruta, Nicole L.
通讯作者：
La Gruta, Nicole L.
影响因子：
5.5
作者：
Kappes, Matthew A.;Sandbulte, Matthew R.;Kehrli, Marcus E., Jr.
通讯作者：
Kehrli, Marcus E., Jr.
影响因子：
5.4
作者：
Pena, Lindomar;Vincent, Amy L.;Perez, Daniel R.
通讯作者：
Perez, Daniel R.
DOI：
10.1073/pnas.1211037109
发表时间：
2012-11-13
影响因子：
11.1
作者：
Li, Qing;Sun, Xiaoman;Gao, George F.
通讯作者：
Gao, George F.