| BMC Veterinary Research | |
| Protective immunity against influenza H5N1 virus challenge in chickens by oral administration of recombinant Lactococcus lactis expressing neuraminidase | |
| Xinqi Ge1  Handing Shu1  Huifeng Jiao1  Daxian Zhao1  Jiexiu Ouyang1  Xiaojue Peng1  Han Lei1  | |
| [1] Department of Biotechnology, College of Life Science, Nanchang University, Jiangxi 330031, China | |
| 关键词: Protective immunity; H5N1 virus; L.lactis/pNZ2103-NA; | |
| Others : 1160675 DOI : 10.1186/s12917-015-0399-4 |
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| received in 2014-09-23, accepted in 2015-03-19, 发布年份 2015 | |
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【 摘 要 】
Background
Highly pathogenic H5N1 avian influenza viruses pose a debilitating pandemic threat in poultry. Current influenza vaccines predominantly focus on hemagglutinin (HA) which anti-HA antibodies are often neutralizing, and are used routinely to assess vaccine immunogenicity. However, Neuraminidase (NA), the other major glycoprotein on the surface of the influenza virus, has historically served as the target for antiviral drug therapy and is much less studied in the context of humoral immunity. The aim of this study was to evaluate the protective immunity of NA based on Lactococcus lactis (L.lactis) expression system against homologous H5N1 virus challenge in a chicken model.
Results
L.lactis/pNZ2103-NA which NA is derived from A/Vietnam/1203/2004 (H5N1) (VN/1203/04) was constructed based on L.lactis constitutive expression system in this study. Chickens vaccinated orally with 1012 colony-forming unit (CFU) of L.lactis/pNZ2103-NA could elicit significant NA-specific serum IgG and mucosa IgA antibodies, as well as neuraminidase inhibition (NI) titer compared with chickens administered orally with saline or L.lactis/pNZ2103 control. Most importantly, the results revealed that chickens administered orally with L.lactis/pNZ2103-NA were completely protected from a lethal H5N1 virus challenge.
Conclusions
The data obtained in the present study indicate that recombinant L.lactis/pNZ2103-NA in the absence of adjuvant can be considered an effective mucosal vaccine against H5N1 infection in chickens via oral administration. Further, these findings support that recombinant L.lactis/pNZ2103-NA can be used to perform mass vaccination in poultry during A/H5N1 pandemic.
【 授权许可】
2015 Lei et al.; licensee BioMed Central.
【 预 览 】
| Files | Size | Format | View |
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| 20150411030051375.pdf | 1154KB | ||
| Figure 3. | 17KB | Image | |
| Figure 2. | 53KB | Image | |
| Figure 1. | 9KB | Image |
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【 参考文献 】
- [1]Subbarao K, Joseph T: Scientific barriers to developing vaccines against avian influenza viruses. Nat Rev Immunol 2007, 7:267-78.
- [2]Pantin-Jackwood MJ, Suarez DL: Vaccination of domestic ducks against H5N1 HPAI: a review. Virus Res 2013, 178:21-34.
- [3]Cha RM, Smith D, Shepherd E, Davis CT, Donis R, Nguyen T: Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines. Vaccine 2013, 31:4953-60.
- [4]Stephenson I, Nicholson KG, Wood JM, Zambon MC, Katz JM: Confronting the avian influenza threat: vaccine development for a potential pandemic. Lancet Infect Dis 2004, 4:499-509.
- [5]Singh N, Pandey A, Mittal SK: Avian influenza pandemic preparedness: developing prepandemic and pandemic vaccines against a moving target. Expert Rev Mol Med 2010, 12:e14.
- [6]Horimoto T, Kawaoka Y: Designing vaccines for pandemic influenza. Curr Top Microbiol Immunol 2009, 333:165-76.
- [7]Easterbrook JD, Schwartzman LM, Gao J, Kash JC, Morens DM, Couzens L, et al.: Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice. Virology 2012, 432:39-44.
- [8]Gao W, Soloff AC, Lu X, Montecalvo A, Nguyen DC, Matsuoka Y, et al.: Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization. J Virol 2006, 80:1959-64.
- [9]Wells JM, Mercenier A: Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nat Rev Microbiol 2008, 6:349-62.
- [10]Lee JS, Shin KS, Pan JG, Kim CJ: Surface displayed viral antigens on salmonella carrier vaccine. Nat Biotechnol 2000, 18:645-8.
- [11]Shata MT, Hone DM: Vaccination with a Shigella DNA vaccine vector induces antigen-specific CD8+ T cells and antiviral protective immunity. J Virol 2001, 75:9665-70.
- [12]Van Huynegem K, Loos M, Steidler L: Immunomodulation by genetically engineered lactic acid bacteria. Front Biosci (Landmark Ed) 2009, 14:4825-35.
- [13]Pontes DS, de Azevedo MS, Chatel JM, Langella P, Azevedo V, Miyoshi A: Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Protein Exp Purif 2011, 79:165-75.
- [14]Lei H, Xu Y, Chen J, Wei X, Lam DM: Immunoprotection against influenza H5N1 virus by oral administration of eneteric coated recombinant Lactococcus lactis mini-capsules. Virology 2010, 407:319-24.
- [15]Lei H, Sheng Z, Ding Q, Chen J, Wei X, Lam DM, et al.: Evaluation of oral immunization with recombinant avian influenza virus HA1 displayed on the Lactococcus lactis surface and combined with the mucosal adjuvant cholera toxin subunit B. Clin Vaccine Immunol 2011, 18:1046-51.
- [16]Lei H, Peng X, Shu H, Zhao D. Intranasal immunization with live recombinant Lactococcus lactis combined with heat-labile toxin B subunit protects chickens from highly pathogenic avian influenza H5N1 virus. J Med Virol. 2014. doi: 10.1002/jmv.23983.
- [17]Wohlbold TJ, Krammer F: In the shadow of hemagglutinin: a growing interest in influenza viral neuraminidase and its role as a vaccine antigen. Viruses 2014, 6:2465-94.
- [18]Rappuoli R, Dormitzer PR: Influenza: options to improve pandemic preparation. Science 2012, 336:1531-3.
- [19]Doyle TM, Hashem AM, Li C, Van Domselaar G, Larocque L, Wang J, et al.: Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Res 2013, 100:567-74.
- [20]Yuki Y, Kiyono H: New generation of mucosal adjuvant for the induction of protective immunity. Rev Med Virol 2003, 13:293-310.
- [21]Bermúdez-Humarán LG: Lactococcus lactis as a live vector for mucosal delivery of therapeutic proteins. Hum Vaccin 2009, 5:264-7.
- [22]Nicholson KG, Wod JM, Zamvon M: Influenza. Lancet 2003, 362:1733-45.
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