tetano
Editor, Senior Moderator
J Virol. 2014 Jun 18. pii: JVI.01468-14. [Epub ahead of print]
All-in-one bacmids: An efficient reverse genetics strategy for influenza A virus vaccines.
Chen H1, Angel M1, Li W1, Finch C1, Gonzalez AS1, Sutton T1, Santos J1, Perez DR2.
Author information
Abstract
Vaccination is the first line of defense against influenza infections, yet influenza vaccine production methods are slow, antiquated, and expensive to effectively reduce the virus' burden during epidemic or pandemic periods. There is a great need for alternative influenza vaccines and vaccination methods with a global scale impact. We demonstrate a strategy to generate influenza A virus in vivo using bacmid DNAs. Compared to the classical reverse genetics system, the "eight-in-one" bacmids (bcmd-RGFlu) showed higher efficiency of virus rescue in various cell types. Using a transfection-based inoculation (TBI) system, intranasal delivery in DBA/2J and Balb/c mice of bcmd-RGFlu plus 293T cells lead to the generation of lethal PR8 virus in vivo. A prime-boost intranasal vaccination strategy using TBI in the context of a bcmd-RGFlu encoding a temperature sensitive H1N1 virus resulted in protection of mice against lethal challenge with the PR8 strain. Taken together, these studies are proof-of-principle to highlight the potential of vaccination against influenza by in vivo reverse genetics.
IMPORTANCE:
Vaccination is the first line of defense against influenza infections. A major drawback in the preparation of influenza vaccines is that production rely on a heavily time consuming process of growing the viruses in eggs. We propose a radical change in the way influenza vaccination is approached in which a recombinant bacmid, a shuttle vector that can be propagated in both E. coli and insect cells, carries an influenza infectious clone (bcmd-RGFlu). Using a surrogate cell system, we show that intranasal delivery of the bcmd-RGFlu results in generation of influenza virus in mice. Furthermore, mice vaccinated with this system were protected against lethal influenza challenge. The study serves as a proof-of-principle of a potentially universal vaccine platform against influenza and other pathogens.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24942589
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24942589
All-in-one bacmids: An efficient reverse genetics strategy for influenza A virus vaccines.
Chen H1, Angel M1, Li W1, Finch C1, Gonzalez AS1, Sutton T1, Santos J1, Perez DR2.
Author information
Abstract
Vaccination is the first line of defense against influenza infections, yet influenza vaccine production methods are slow, antiquated, and expensive to effectively reduce the virus' burden during epidemic or pandemic periods. There is a great need for alternative influenza vaccines and vaccination methods with a global scale impact. We demonstrate a strategy to generate influenza A virus in vivo using bacmid DNAs. Compared to the classical reverse genetics system, the "eight-in-one" bacmids (bcmd-RGFlu) showed higher efficiency of virus rescue in various cell types. Using a transfection-based inoculation (TBI) system, intranasal delivery in DBA/2J and Balb/c mice of bcmd-RGFlu plus 293T cells lead to the generation of lethal PR8 virus in vivo. A prime-boost intranasal vaccination strategy using TBI in the context of a bcmd-RGFlu encoding a temperature sensitive H1N1 virus resulted in protection of mice against lethal challenge with the PR8 strain. Taken together, these studies are proof-of-principle to highlight the potential of vaccination against influenza by in vivo reverse genetics.
IMPORTANCE:
Vaccination is the first line of defense against influenza infections. A major drawback in the preparation of influenza vaccines is that production rely on a heavily time consuming process of growing the viruses in eggs. We propose a radical change in the way influenza vaccination is approached in which a recombinant bacmid, a shuttle vector that can be propagated in both E. coli and insect cells, carries an influenza infectious clone (bcmd-RGFlu). Using a surrogate cell system, we show that intranasal delivery of the bcmd-RGFlu results in generation of influenza virus in mice. Furthermore, mice vaccinated with this system were protected against lethal influenza challenge. The study serves as a proof-of-principle of a potentially universal vaccine platform against influenza and other pathogens.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24942589
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24942589