Generation of a live attenuated influenza A vaccine by proteolysis targeting

Si, Longlong1; Shen, Quan1; Li, Jing1; Chen, Li1; Shen, Jinying1; Xiao, Xue1; Bai, Haiqing2; Feng, Tang3; Ye, Adam Yongxin4; Li, Le1; Zhang, Chunhe1,3; Li, Zhen1; Wang, Ping1; Oh, Crystal Yuri5; Nurani, Atiq6; Niu, Siwen7; Zhang, Chengxin8; Wei, Xiaoqiong8; Yuan, Wanqiong9,10,11; Liao, Hao12; Huang, Xiaojie13; Wang, Ning13; Tian, Wen-xia14; Tian, Hongwei15; Li, Li4; Liu, Xiaoheng3; Plebani, Roberto16

2022-07-01

10.1038/s41587-022-01381-4

NATURE BIOTECHNOLOGY   Impact Factor & Quartile

1087-0156

1546-1696

["Influenza virus is attenuated for vaccine production using PROTAC degradation technology.","The usefulness of live attenuated virus vaccines has been limited by suboptimal immunogenicity, safety concerns or cumbersome manufacturing processes and techniques. Here we describe the generation of a live attenuated influenza A virus vaccine using proteolysis-targeting chimeric (PROTAC) technology to degrade viral proteins via the endogenous ubiquitin-proteasome system of host cells. We engineered the genome of influenza A viruses in stable cell lines engineered for virus production to introduce a conditionally removable proteasome-targeting domain, generating fully infective PROTAC viruses that were live attenuated by the host protein degradation machinery upon infection. In mouse and ferret models, PROTAC viruses were highly attenuated and able to elicit robust and broad humoral, mucosal and cellular immunity against homologous and heterologous virus challenges. PROTAC-mediated attenuation of viruses may be broadly applicable for generating live attenuated vaccines."]

SCI ; EI

English

NI Journal Papers

Others

National Natural Science Foundation of China[11932014,81802456] ; China-U.S. Collaborative Program on Emerging and Re-emerging Infectious Diseases[E2900901-02] ; Guangdong Basic and Applied Basic Research Foundation[2019A1515110615] ; Natural Science Foundation Program of Shaanxi Province of China[2020JQ-545] ; China Postdoctoral Science Foundation[2019TQ0206]

Biotechnology & Applied Microbiology

Biotechnology & Applied Microbiology

WOS:000820564100001

NATURE PORTFOLIO

20222712326461

Cell culture ; Machinery ; Proteins ; Proteolysis ; Vaccines

Medicine and Pharmacology:461.6 ; Biology:461.9 ; Biochemistry:801.2 ; Organic Compounds:804.1

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, CAS Key Lab Quantitat Engn Biol, Shenzhen, Peoples R China
2.Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
3.Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Inst Biomed Engn, Chengdu, Peoples R China
4.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA
5.Pfizer Inc, Rare Dis Res Unit, Cambridge, MA USA
6.Jnana Therapeut, Boston, MA USA
7.State Ocean Adm, Inst Oceanog 3, Xiamen, Peoples R China
8.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
9.Peking Univ Third Hosp, Dept Orthoped, Beijing, Peoples R China
10.Beijing Key Lab Spinal Dis, Beijing, Peoples R China
11.Engn Res Ctr Bone & Joint Precis Med, Beijing, Peoples R China
12.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Dept Clin Lab, Shenzhen, Peoples R China
13.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China
14.Shanxi Agr Univ, Coll Vet Med, Jinzhong, Peoples R China
15.Xi An Jiao Tong Univ, Natl & Local Joint Engn Res Ctr Biodiag & Biother, Affiliated Hosp 2, Xian, Peoples R China
16.G dAnnunzio Univ Chieti Pescara, Ctr Adv Studies & Technol CAST, Dept Med Oral & Biotechnol Sci, Chieti, Italy

Si, Longlong,Shen, Quan,Li, Jing,et al. Generation of a live attenuated influenza A vaccine by proteolysis targeting[J]. NATURE BIOTECHNOLOGY,2022,40(9):1370-1377.

Si, Longlong.,Shen, Quan.,Li, Jing.,Chen, Li.,Shen, Jinying.,...&Plebani, Roberto.(2022).Generation of a live attenuated influenza A vaccine by proteolysis targeting.NATURE BIOTECHNOLOGY,40(9),1370-1377.

Si, Longlong,et al."Generation of a live attenuated influenza A vaccine by proteolysis targeting".NATURE BIOTECHNOLOGY 40.9(2022):1370-1377.