title: Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell dependent, cross-clade protection against H5N1 influenza virus in mice.
abstract: H5N1, highly pathogenic avian influenza poses, a threat to animal and human health. Rapid changes in H5N1 viruses require periodic reformulation of the conventional strain-matched vaccines, thus emphasizing the need for a broadly protective influenza vaccine. Here, we constructed BV-Dual-3M2e-LTB, a recombinant baculovirus based on baculovirus display and BacMam technology. BV-Dual-3M2e-LTB harbors a gene cassette expressing three tandem copies of the highly conserved extracellular domain of influenza M2 protein (M2e) and the mucosal adjuvant, LTB. We showed that BV-Dual-3M2e-LTB displayed the target protein (M2e/LTB) on the baculoviral surface and expressed it in transduced mammalian cells. BV-Dual-3M2e-LTB, when delivered nasally in mice, was highly immunogenic and induced superior levels of anti-M2e IgA than the non-adjuvanted baculovirus (BV-Dual-3M2e). Importantly, after challenge with different H5N1 clades (clade 0, 2.3.2.1, 2.3.4 and 4), mice inoculated with BV-Dual-3M2e-LTB displayed improved survival and decreased lung virus shedding compared with mice inoculated with BV-Dual-3M2e. The enhanced protection from BV-Dual-3M2e-LTB is mediated by T cell immunity and is primarily based on CD8(+) T cells, while mucosal antibodies alone were insufficient for protection from lethal H5N1 challenge. These results suggest that BV-Dual-3M2e-LTB has potential to protect against a broad range of H5N1 strains thereby providing a novel direction for developing broadly protective vaccines based on cellular immunity.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Fan
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
authors.forename: Jian-Ni
authors.initials: JN
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China. Electronic address: mliao@scau.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016367:Baculoviridae; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection; D005260:Female; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*; D017201:Virus Shedding; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Baculovirus; H5N1; Influenza; LTB; M2e