tetano
Editor, Senior Moderator
J Control Release. 2015 Apr 6. pii: S0168-3659(15)00219-9. doi: 10.1016/j.jconrel.2015.04.001. [Epub ahead of print]
[h=1]Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA.[/h] Li J[SUP]1[/SUP], Ar?valo MT[SUP]1[/SUP], Diaz-Ar?valo D[SUP]1[/SUP], Chen Y[SUP]1[/SUP], Choi JG[SUP]1[/SUP], Zeng M[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Vaccination with live attenuated vaccines (LAVs) is an effective way for prevention of infectious disease. While several methods are employed to create them, efficacy and safety are still a challenge. In this study, we evaluated the feasibility of creating a self-attenuated RNA virus expressing a functional species-specific artificial microRNA. Using influenza virus as a model, we produced an attenuated virus carrying a mammalian-specific miR-93 expression cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA from an insertion site within the non-structural (NS) gene segment. The resulting engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and functional artificial microRNA against NP in mammalian cells, but not in avian cells. Furthermore, PR8-amiR-93NP was attenuated by 10[SUP]4[/SUP] fold in mice compared with its wild-type counterpart. Importantly, intranasal immunization with PR8-amiR-93NP conferred cross-protective immunity against heterologous influenza virus strains. In short, this method provides a safe and effective platform for creation of live attenuated RNA viral vaccines.
Copyright ? 2015. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Artificial microRNA; Cross-protection; Influenza virus; Live attenuated vaccine; Safety
PMID: 25858415 [PubMed - as supplied by publisher]
[h=1]Generation of a safe and effective live viral vaccine by virus self-attenuation using species-specific artificial microRNA.[/h] Li J[SUP]1[/SUP], Ar?valo MT[SUP]1[/SUP], Diaz-Ar?valo D[SUP]1[/SUP], Chen Y[SUP]1[/SUP], Choi JG[SUP]1[/SUP], Zeng M[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Vaccination with live attenuated vaccines (LAVs) is an effective way for prevention of infectious disease. While several methods are employed to create them, efficacy and safety are still a challenge. In this study, we evaluated the feasibility of creating a self-attenuated RNA virus expressing a functional species-specific artificial microRNA. Using influenza virus as a model, we produced an attenuated virus carrying a mammalian-specific miR-93 expression cassette that expresses a viral nucleoprotein (NP)-specific artificial microRNA from an insertion site within the non-structural (NS) gene segment. The resulting engineered live-attenuated influenza virus, PR8-amiR-93NP, produced mature and functional artificial microRNA against NP in mammalian cells, but not in avian cells. Furthermore, PR8-amiR-93NP was attenuated by 10[SUP]4[/SUP] fold in mice compared with its wild-type counterpart. Importantly, intranasal immunization with PR8-amiR-93NP conferred cross-protective immunity against heterologous influenza virus strains. In short, this method provides a safe and effective platform for creation of live attenuated RNA viral vaccines.
Copyright ? 2015. Published by Elsevier B.V.
[h=4]KEYWORDS:[/h] Artificial microRNA; Cross-protection; Influenza virus; Live attenuated vaccine; Safety
PMID: 25858415 [PubMed - as supplied by publisher]