tetano
Editor, Senior Moderator
Int J Pharm
. 2021 Dec 6;121325.
doi: 10.1016/j.ijpharm.2021.121325. Online ahead of print.
A new self-attenuated therapeutic influenza vaccine that uses host cell-restricted attenuation by artificial microRNAs
Ke Wen[SUP] 1 [/SUP], Haiyan Wang[SUP] 2 [/SUP], Yanping Chen[SUP] 1 [/SUP], Huixiao Yang[SUP] 2 [/SUP], Zhichao Zheng[SUP] 2 [/SUP], Yongyong Yan[SUP] 2 [/SUP], Realivazquez Adilene[SUP] 3 [/SUP], Mingtao Zeng[SUP] 4 [/SUP]
Affiliations
Abstract
New strategies are urgently needed for developing vaccines and/or anti-viral drugs against influenza viruses, because antigenic shift and drift inevitably occurs in circulating strains each year, and new strains resistant to anti-viral drugs have recently emerged. In our study, we designed and incorporated artificial microRNAs (amiRNAs) into the NA segment of rescued influenza viruses to separately target two host genes, Cdc2-like kinase 1 (CLK1) and SON DNA binding protein (SON), which were found to play an essential role in virus replication. Mouse epithelial fibroblast (MEF) or human lung carcinoma A549 cells infected with engineered influenza PR8 viruses expressing amiR-30CLK1 (PR8-amiR-30CLK1) or amiR-93SON (PR8-amiR-93SON) had reduced expression of host proteins CLK1 and SON, respectively. All engineered influenza viruses functioned as attenuated vaccines, induced significantly higher antibody responses, and provided greater protective efficacy. In addition, they were found to be safe, based on the mouse weight changes and clinical signs observed. In contrast to the engineered viruses targeting SON, mice treated with engineered viruses targeting CLK1 recovered from weight loss and survived lethal infection by 6 h after lethal-dose PR8 infection, suggesting that our PR8-amiR-30CLK1 self-attenuated influenza virus (SAIV) could be used as a new therapeutic influenza vaccine.
Keywords: Cdc2-like kinase 1; SON DNA-binding protein; artificial microRNA; intranasal delivery; live attenuated influenza vaccine; therapeutic vaccine.
. 2021 Dec 6;121325.
doi: 10.1016/j.ijpharm.2021.121325. Online ahead of print.
A new self-attenuated therapeutic influenza vaccine that uses host cell-restricted attenuation by artificial microRNAs
Ke Wen[SUP] 1 [/SUP], Haiyan Wang[SUP] 2 [/SUP], Yanping Chen[SUP] 1 [/SUP], Huixiao Yang[SUP] 2 [/SUP], Zhichao Zheng[SUP] 2 [/SUP], Yongyong Yan[SUP] 2 [/SUP], Realivazquez Adilene[SUP] 3 [/SUP], Mingtao Zeng[SUP] 4 [/SUP]
Affiliations
- PMID: 34883209
- DOI: 10.1016/j.ijpharm.2021.121325
Abstract
New strategies are urgently needed for developing vaccines and/or anti-viral drugs against influenza viruses, because antigenic shift and drift inevitably occurs in circulating strains each year, and new strains resistant to anti-viral drugs have recently emerged. In our study, we designed and incorporated artificial microRNAs (amiRNAs) into the NA segment of rescued influenza viruses to separately target two host genes, Cdc2-like kinase 1 (CLK1) and SON DNA binding protein (SON), which were found to play an essential role in virus replication. Mouse epithelial fibroblast (MEF) or human lung carcinoma A549 cells infected with engineered influenza PR8 viruses expressing amiR-30CLK1 (PR8-amiR-30CLK1) or amiR-93SON (PR8-amiR-93SON) had reduced expression of host proteins CLK1 and SON, respectively. All engineered influenza viruses functioned as attenuated vaccines, induced significantly higher antibody responses, and provided greater protective efficacy. In addition, they were found to be safe, based on the mouse weight changes and clinical signs observed. In contrast to the engineered viruses targeting SON, mice treated with engineered viruses targeting CLK1 recovered from weight loss and survived lethal infection by 6 h after lethal-dose PR8 infection, suggesting that our PR8-amiR-30CLK1 self-attenuated influenza virus (SAIV) could be used as a new therapeutic influenza vaccine.
Keywords: Cdc2-like kinase 1; SON DNA-binding protein; artificial microRNA; intranasal delivery; live attenuated influenza vaccine; therapeutic vaccine.