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Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell dependent, cross-clade protection against H5N1 influenza virus in mice.
Vaccine. 2016 Jan 27; 34(5):622-629.V

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+Show Affiliations

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.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.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.College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.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.College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26724200

Citation

Zhang, Jie, et al. "Recombinant Baculovirus Vaccine Containing Multiple M2e and Adjuvant LTB Induces T Cell Dependent, Cross-clade Protection Against H5N1 Influenza Virus in Mice." Vaccine, vol. 34, no. 5, 2016, pp. 622-629.
Zhang J, Fan HY, Zhang Z, et al. Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell dependent, cross-clade protection against H5N1 influenza virus in mice. Vaccine. 2016;34(5):622-629.
Zhang, J., Fan, H. Y., Zhang, Z., Zhang, J., Zhang, J., Huang, J. N., Ye, Y., & Liao, M. (2016). Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell dependent, cross-clade protection against H5N1 influenza virus in mice. Vaccine, 34(5), 622-629. https://doi.org/10.1016/j.vaccine.2015.12.039
Zhang J, et al. Recombinant Baculovirus Vaccine Containing Multiple M2e and Adjuvant LTB Induces T Cell Dependent, Cross-clade Protection Against H5N1 Influenza Virus in Mice. Vaccine. 2016 Jan 27;34(5):622-629. PubMed PMID: 26724200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant baculovirus vaccine containing multiple M2e and adjuvant LTB induces T cell dependent, cross-clade protection against H5N1 influenza virus in mice. AU - Zhang,Jie, AU - Fan,Hui-Ying, AU - Zhang,Zhen, AU - Zhang,Juan, AU - Zhang,Jiao, AU - Huang,Jian-Ni, AU - Ye,Yu, AU - Liao,Ming, Y1 - 2015/12/23/ PY - 2015/05/19/received PY - 2015/10/19/revised PY - 2015/12/15/accepted PY - 2016/1/3/entrez PY - 2016/1/3/pubmed PY - 2016/9/30/medline KW - Baculovirus KW - H5N1 KW - Influenza KW - LTB KW - M2e SP - 622 EP - 629 JF - Vaccine JO - Vaccine VL - 34 IS - 5 N2 - 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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/26724200/Recombinant_baculovirus_vaccine_containing_multiple_M2e_and_adjuvant_LTB_induces_T_cell_dependent_cross_clade_protection_against_H5N1_influenza_virus_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(15)01836-8 DB - PRIME DP - Unbound Medicine ER -