tetano
Editor, Senior Moderator
J Gen Virol. 2014 Jan 15. doi: 10.1099/vir.0.059253-0. [Epub ahead of print]
Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the hemagglutinin of pandemic swine origin H1N1 influenza A virus.
Klingbeil K, Lange E, Teifke JP, Mettenleiter TC, Fuchs W.
Author information
Abstract
Pigs can be severely harmed by flu, and represent important reservoir hosts, in which new human pathogens like the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszkys disease of swine, pseudorabies virus (PrV) strain Bartha, to serve as vector for the expression of hemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.
KEYWORDS:
hemagglutinin, pseudorabies virus, swine origin influenza A virus, vectored live-virus vaccine
PMID:
24431235
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24431235
Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the hemagglutinin of pandemic swine origin H1N1 influenza A virus.
Klingbeil K, Lange E, Teifke JP, Mettenleiter TC, Fuchs W.
Author information
Abstract
Pigs can be severely harmed by flu, and represent important reservoir hosts, in which new human pathogens like the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszkys disease of swine, pseudorabies virus (PrV) strain Bartha, to serve as vector for the expression of hemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.
KEYWORDS:
hemagglutinin, pseudorabies virus, swine origin influenza A virus, vectored live-virus vaccine
PMID:
24431235
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24431235