title: Cross-protective efficacy of baculovirus displayed hemagglutinin against highly pathogenic influenza H7 subtypes.
abstract: The outbreak of human infections with avian-origin H7N9 influenza has raised global concerns about a potential human pandemic. Therefore, the generation of simple and reliable newer vaccines is high priority for pandemic preparedness. In this study, we aimed to develop a recombinant vaccine by expressing HA of H7N9 (A/Shanghai/2/2013) on the surface of baculovirus (BacHA). Further, live or inactive form of BacHA (H7N9) vaccine was immunized twice either intranasally or subcutaneously into mice. The immunogenicity and cross-protective efficacy of the BacHA (H7N9) vaccine was assessed against H7N9 or H7N7 subtype challenge. The results showed that mice immunized subcutaneously with adjuvanted inactive BacHA (H7N9) induced robust cross-neutralizing antibody responses against H7 subtypes (H7N9, H7N7 and H7N3) compared to subcutaneous or intranasal immunization of live BacHA. In contrast, mice immunized intranasally with live BacHA stimulated higher HA-specific mucosal IgA levels in the upper airways, the port of virus entry. Also, intranasal immunization of BacHA of either H7N9 or H7N7 completely protected against 5 MLD50 of both H7N9 and H7N7 infections. An overall study revealed that intranasal administration of HA expressed on the baculovirus envelope is alternative way to prime the immune system against influenza infection during a pandemic situation.
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Mookkan
authors.initials: M
authors.lastname: Prabakaran
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Subaschandrabose Rajesh
authors.initials: SR
authors.lastname: Kumar
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Kattur Venkatachalam Ashok
authors.initials: KV
authors.lastname: Raj
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore; Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Xiapeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Fang
authors.initials: F
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China. Electronic address: jyzhu@zju.edu.cn.
authors.forename: JiYong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore; Department of Microbiology, Faculty of Medicine, National University of Singapore, Singapore. Electronic address: kwang@tll.org.sg.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kwang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D056738:Cross Protection; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057920:Influenza A Virus, H7N3 Subtype / Q000276:immunology / Q000502:physiology; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology / Q000502:physiology; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus
keywords: Baculovirus displayed HA; H7N9; Intranasal immunization; Mucosal immunity