Mary Wilson
Well-known member
Posted January 16, 2025
doi: https://doi.org/10.1101/2025.01.15.633174
Marion Stettler123, Stefan Hoby1, Christian Wenker4, Fabia Wyss4, Elisabeth Heiderich1, Lisa Butticaz2, Nicolas Ruggli23, Karin Darpel23 and Gert Zimmer23*
Abstract
Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 (clade 2.3.4.4b) have spread worldwide and caused the death of hundreds of millions of wild birds and domestic poultry. Moreover, spill over of H5N1 HPAIV from infected birds to more than 50 different mammalian species including humans has been recorded. While, licensed vaccines for protection of avian or mammalian species are not yet available, a few candidate vaccines are being trialled. Here, we report on the experimental vaccination of chickens and captive wild birds using a propagation-defective vesicular stomatitis virus (VSV), in which the essential envelope glycoprotein (G) protein gene was replaced by a modified hemagglutinin gene derived from a clade 2.3.4.4b H5N1 isolated in 2022 in the animal park of Bern, Switzerland. VSVΔG(H5[SUB]mb[/SUB]) was produced on helper cells providing the VSV G protein in trans. Specific pathogen-free (SPF) chickens that were immunized twice via the intramuscular route with adjuvant-free VSVΔG(H5[SUB]mb[/SUB]) replicon particles induced high levels of virus-neutralizing serum antibodies and were fully protected against lethal infection by H5N1 HPAIV (clade 2.3.4.4b). Notably, immunized animals did not shed challenge virus from the respiratory or gastrointestinal tract, suggesting that herd immunity can be achieved. The same vaccine was used to immunize a total of 317 captive wild birds at Bern Animal Park and Zoo Basel, representing 24 different species. No vaccine-associated side effects were observed. Birds without previous contact to H5Nx viruses produced high to very high H5-specific neutralizing antibody titers following the second immunization, while birds showing H5-specific antibodies prior to vaccination, already developed high neutralising antibody titers after a single immunization. One year after vaccination, most animals still showed significant neutralizing antibody titers, indicating that VSVΔG(H5[SUB]mb[/SUB]) is able to induce a long-lasting protective immune response. Our results indicate that VSVΔG(H5[SUB]mb[/SUB]) is an extraordinary safe and highly efficacious vaccine to stop H5N1 replication in various avian species.
https://www.biorxiv.org/content/10.1101/2025.01.15.633174v1.full
doi: https://doi.org/10.1101/2025.01.15.633174
Marion Stettler123, Stefan Hoby1, Christian Wenker4, Fabia Wyss4, Elisabeth Heiderich1, Lisa Butticaz2, Nicolas Ruggli23, Karin Darpel23 and Gert Zimmer23*
Abstract
Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 (clade 2.3.4.4b) have spread worldwide and caused the death of hundreds of millions of wild birds and domestic poultry. Moreover, spill over of H5N1 HPAIV from infected birds to more than 50 different mammalian species including humans has been recorded. While, licensed vaccines for protection of avian or mammalian species are not yet available, a few candidate vaccines are being trialled. Here, we report on the experimental vaccination of chickens and captive wild birds using a propagation-defective vesicular stomatitis virus (VSV), in which the essential envelope glycoprotein (G) protein gene was replaced by a modified hemagglutinin gene derived from a clade 2.3.4.4b H5N1 isolated in 2022 in the animal park of Bern, Switzerland. VSVΔG(H5[SUB]mb[/SUB]) was produced on helper cells providing the VSV G protein in trans. Specific pathogen-free (SPF) chickens that were immunized twice via the intramuscular route with adjuvant-free VSVΔG(H5[SUB]mb[/SUB]) replicon particles induced high levels of virus-neutralizing serum antibodies and were fully protected against lethal infection by H5N1 HPAIV (clade 2.3.4.4b). Notably, immunized animals did not shed challenge virus from the respiratory or gastrointestinal tract, suggesting that herd immunity can be achieved. The same vaccine was used to immunize a total of 317 captive wild birds at Bern Animal Park and Zoo Basel, representing 24 different species. No vaccine-associated side effects were observed. Birds without previous contact to H5Nx viruses produced high to very high H5-specific neutralizing antibody titers following the second immunization, while birds showing H5-specific antibodies prior to vaccination, already developed high neutralising antibody titers after a single immunization. One year after vaccination, most animals still showed significant neutralizing antibody titers, indicating that VSVΔG(H5[SUB]mb[/SUB]) is able to induce a long-lasting protective immune response. Our results indicate that VSVΔG(H5[SUB]mb[/SUB]) is an extraordinary safe and highly efficacious vaccine to stop H5N1 replication in various avian species.
https://www.biorxiv.org/content/10.1101/2025.01.15.633174v1.full