Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge. Issue 14 (1st April 2021)

• Record Type: Journal Article
• Authors: Lee, Jinhwa; Li, Yonghai; Li, Yuhao; Cino-Ozuna, A. Giselle; Duff, Michael; Lang, Yuekun; Ma, Jingjiao; Sunwoo, Sunyoung; Richt, Juergen A.; Ma, Wenjun
• Is Part Of: Vaccine. Volume 39:Issue 14(2021)
• Page Start: 1943
• Page End: 1950
• Publication Date: 2021-04-01
• Subjects: Swine influenza vaccine -- Bat influenza virus vectored live vaccine -- Cross-protection -- Heterologous virus challenge -- Safety and efficacy; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.02.077
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlight: Chimeric bat influenza viruses as vaccines show no reassortment with classical influenza viruses. Novel vaccines reduce virus replication and pathology of pigs infected with a heterologous virus. Novel vaccines reduce virus nasal shedding in immunized and challenged pigs. Novel vaccines induce robust mucosal and T-cell immune responses in pigs without VAERD. Bat influenza vectored vaccines are effective and safe without VAERD and reassortment. Abstract: 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.