tetano
Editor, Senior Moderator
J Virol. 2010 Oct 20. [Epub ahead of print]
Modifications in the polymerase genes of a swine-like triple reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses.
Pena L, Vincent AL, Ye J, Ciacci-Zanella JR, Angel M, Lorusso A, Gauger PC, Janke BH, Loving CL, Perez DR.
Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA; Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA; Laborat?rio de Virologia, Embrapa Su?nos e Aves, Conc?rdia, Santa Catarina, Brazil; Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA.
Abstract
On June 11, 2009 the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) is the predominant influenza strain in the human population. It has also crossed the species barriers and infected turkeys and swine in several countries. Thus, the development of a vaccine that is effective in multiple animal species is urgently needed. We have previously demonstrated that introduction of temperature-sensitive mutations in the PB2 and PB1 genes of an avian H9N2 combined with the insertion of an HA tag in PB1 resulted in an attenuated (att) vaccine backbone for both chickens and mice. Because the new pandemic strain is a triple reassortant (TR) virus, we chose a swine-like TR virus isolate, A/turkey/OH/313053/04 (H3N2) (ty/04), to introduce the double attenuating modifications with the goal of producing live attenuated influenza vaccines (LAIV). This genetically modified backbone had impaired polymerase activity and restricted virus growth at elevated temperatures. In vivo characterization of two H1N1 vaccine candidates generated using the ty/04 att backbone demonstrated that this vaccine is highly attenuated in mice as indicated by the absence of signs of disease, limited replication and minimum histopathological alterations in the respiratory tract. A single immunization with the ty/04 att-based vaccines conferred complete protection against a lethal H1N1pdm infection in mice. More importantly, vaccination of pigs with a ty/04 att-H1N1 vaccine candidate resulted in sterilizing immunity upon an aggressive intratracheal challenge with the 2009 H1N1 pandemic virus. Our studies highlight the safety of the ty/04 att vaccine platform and its potential as a master donor strain for the generation of live attenuated vaccines for humans and livestock.
PMID: 20962084 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20962084
Modifications in the polymerase genes of a swine-like triple reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses.
Pena L, Vincent AL, Ye J, Ciacci-Zanella JR, Angel M, Lorusso A, Gauger PC, Janke BH, Loving CL, Perez DR.
Department of Veterinary Medicine, University of Maryland, College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA; Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA; Laborat?rio de Virologia, Embrapa Su?nos e Aves, Conc?rdia, Santa Catarina, Brazil; Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA.
Abstract
On June 11, 2009 the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) is the predominant influenza strain in the human population. It has also crossed the species barriers and infected turkeys and swine in several countries. Thus, the development of a vaccine that is effective in multiple animal species is urgently needed. We have previously demonstrated that introduction of temperature-sensitive mutations in the PB2 and PB1 genes of an avian H9N2 combined with the insertion of an HA tag in PB1 resulted in an attenuated (att) vaccine backbone for both chickens and mice. Because the new pandemic strain is a triple reassortant (TR) virus, we chose a swine-like TR virus isolate, A/turkey/OH/313053/04 (H3N2) (ty/04), to introduce the double attenuating modifications with the goal of producing live attenuated influenza vaccines (LAIV). This genetically modified backbone had impaired polymerase activity and restricted virus growth at elevated temperatures. In vivo characterization of two H1N1 vaccine candidates generated using the ty/04 att backbone demonstrated that this vaccine is highly attenuated in mice as indicated by the absence of signs of disease, limited replication and minimum histopathological alterations in the respiratory tract. A single immunization with the ty/04 att-based vaccines conferred complete protection against a lethal H1N1pdm infection in mice. More importantly, vaccination of pigs with a ty/04 att-H1N1 vaccine candidate resulted in sterilizing immunity upon an aggressive intratracheal challenge with the 2009 H1N1 pandemic virus. Our studies highlight the safety of the ty/04 att vaccine platform and its potential as a master donor strain for the generation of live attenuated vaccines for humans and livestock.
PMID: 20962084 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20962084