Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge

被引：13
作者：
Lee, Jinhwa [1 ]
Li, Yonghai [1 ]
Li, Yuhao [1 ]
Cino-Ozuna, A. Giselle [1 ]
Duff, Michael [1 ]
Lang, Yuekun [1 ]
Ma, Jingjiao [1 ]
Sunwoo, Sunyoung [1 ]
Richt, Juergen A. [1 ]
Ma, Wenjun [1 ,2 ,3 ]
机构：
[1] Kansas State Univ, Coll Vet Med, Dept Diagnost Med Pathobiol, Manhattan, KS USA
[2] Univ Missouri, Coll Vet Med, Dept Vet Pathobiol, Columbia, MO USA
[3] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO USA
来源：
VACCINE | 2021年 / 39卷 / 14期
关键词：
Swine influenza vaccine; Bat influenza virus vectored live vaccine; Cross-protection; Heterologous virus challenge; Safety and efficacy; ENHANCED RESPIRATORY-DISEASE; T-CELL IMMUNITY; A VIRUS; IN-VIVO; SWINE; HEMAGGLUTININ; INFECTION; EFFICACY; PATHOGENICITY; RESPONSES;
D O I：
10.1016/j.vaccine.2021.02.077
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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-gamma 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. (C) 2021 Elsevier Ltd. All rights reserved.
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页码：1943 / 1950
页数：8
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