tetano
Editor, Senior Moderator
J Virol. 2014 Dec 24. pii: JVI.03246-14. [Epub ahead of print]
[h=1]A Viable Recombinant Rhabdovirus Lacking Its Glycoprotein Gene and Expressing Influenza Hemagglutinin and Neuraminidase Is a Potent Influenza Vaccine.[/h] Ryder AB[SUP]1[/SUP], Buonocore L[SUP]2[/SUP], Vogel L[SUP]3[/SUP], Nachbagauer R[SUP]4[/SUP], Krammer F[SUP]5[/SUP], Rose JK[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The emergence of novel influenza viruses that cause devastating human disease is an ongoing threat, and serves as an impetus for continued development of novel approaches to influenza vaccines. Influenza vaccine development has traditionally focused on producing humoral and/or cell-mediated immunity, often against the viral surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Here, we describe a new vaccine candidate that utilizes a replication-defective vesicular stomatitis virus (VSV) vector backbone that lacks the native G surface glycoprotein gene (VSVΔG). The expression of the H5 HA of an H5N1 highly pathogenic avian influenza virus (HPAIV), A/Vietnam/1203/04 (VN1203), and the NA of the mouse-adapted H1N1 influenza virus, A/Puerto Rico/8/34 (PR8), in the VSVΔG vector restored the ability of the recombinant virus to replicate in cell culture, without the requirement for addition of trypsin. We show here that this recombinant virus vaccine candidate was non-pathogenic in mice when given by either intramuscular or intranasal routes of immunization, and that in vivo replication of the VSVΔG-H5N1 virus is profoundly attenuated. It also provided protection against lethal H5N1 infection after a single dose. This novel approach to vaccination against HPAIVs may be widely applicable to other emerging strains of influenza.
[h=4]IMPORTANCE:[/h] Preparation for a potentially catastrophic influenza pandemic requires novel influenza vaccines that are safe, can be produced and administered quickly, and are effective, both soon after administration, and for a long duration. We have created a new influenza vaccine that utilizes an attenuated vesicular stomatitis virus (VSV) vector, to deliver and express influenza proteins against which vaccinated animals develop potent antibody responses. The influenza hemagglutinin and neuraminidase proteins, expressed on the surface of VSV viral particles, allowed this vaccine to grow in cell culture, and induced a potent antibody response in mice that was effective against infection with a lethal influenza virus. The mice showed no adverse reactions to the vaccine, and they were protected against an otherwise lethal influenza infection after only 14 days post-vaccination, and after as many as 140 days post-vaccination. The ability to rapidly produce this safe and effective vaccine in cell culture is additionally advantageous.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID: 25540378 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25540378
[h=1]A Viable Recombinant Rhabdovirus Lacking Its Glycoprotein Gene and Expressing Influenza Hemagglutinin and Neuraminidase Is a Potent Influenza Vaccine.[/h] Ryder AB[SUP]1[/SUP], Buonocore L[SUP]2[/SUP], Vogel L[SUP]3[/SUP], Nachbagauer R[SUP]4[/SUP], Krammer F[SUP]5[/SUP], Rose JK[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The emergence of novel influenza viruses that cause devastating human disease is an ongoing threat, and serves as an impetus for continued development of novel approaches to influenza vaccines. Influenza vaccine development has traditionally focused on producing humoral and/or cell-mediated immunity, often against the viral surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Here, we describe a new vaccine candidate that utilizes a replication-defective vesicular stomatitis virus (VSV) vector backbone that lacks the native G surface glycoprotein gene (VSVΔG). The expression of the H5 HA of an H5N1 highly pathogenic avian influenza virus (HPAIV), A/Vietnam/1203/04 (VN1203), and the NA of the mouse-adapted H1N1 influenza virus, A/Puerto Rico/8/34 (PR8), in the VSVΔG vector restored the ability of the recombinant virus to replicate in cell culture, without the requirement for addition of trypsin. We show here that this recombinant virus vaccine candidate was non-pathogenic in mice when given by either intramuscular or intranasal routes of immunization, and that in vivo replication of the VSVΔG-H5N1 virus is profoundly attenuated. It also provided protection against lethal H5N1 infection after a single dose. This novel approach to vaccination against HPAIVs may be widely applicable to other emerging strains of influenza.
[h=4]IMPORTANCE:[/h] Preparation for a potentially catastrophic influenza pandemic requires novel influenza vaccines that are safe, can be produced and administered quickly, and are effective, both soon after administration, and for a long duration. We have created a new influenza vaccine that utilizes an attenuated vesicular stomatitis virus (VSV) vector, to deliver and express influenza proteins against which vaccinated animals develop potent antibody responses. The influenza hemagglutinin and neuraminidase proteins, expressed on the surface of VSV viral particles, allowed this vaccine to grow in cell culture, and induced a potent antibody response in mice that was effective against infection with a lethal influenza virus. The mice showed no adverse reactions to the vaccine, and they were protected against an otherwise lethal influenza infection after only 14 days post-vaccination, and after as many as 140 days post-vaccination. The ability to rapidly produce this safe and effective vaccine in cell culture is additionally advantageous.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID: 25540378 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25540378