date: 2023-03-14T04:38:41Z pdf:unmappedUnicodeCharsPerPage: 0 pdf:PDFVersion: 1.7 pdf:docinfo:title: Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model xmp:CreatorTool: LaTeX with hyperref Keywords: VPM1002; Bacille Calmette-Guérin; immune response; tuberculosis vaccine; goat model access_permission:modify_annotations: true access_permission:can_print_degraded: true subject: A more effective vaccine against tuberculosis than Bacille Calmette-Guérin (BCG) is urgently needed. BCG derived recombinant VPM1002 has been found to be more efficacious and safer than the parental strain in mice models. Newer candidates, such as VPM1002 pdx1 (PDX) and VPM1002 nuoG (NUOG), were generated to further improve the safety profile or efficacy of the vaccine. Herein, we assessed the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, in juvenile goats. Vaccination did not affect the goats? health in regards to clinical/hematological features. However, all three tested vaccine candidates and BCG induced granulomas at the site of injection, with some of the nodules developing ulcerations approximately one month post-vaccination. Viable vaccine strains were cultured from the injection site wounds in a few NUOG- and PDX- vaccinated animals. At necropsy (127 days post-vaccination), BCG, VPM1002, and NUOG, but not PDX, still persisted at the injection granulomas. All strains, apart from NUOG, induced granuloma formation only in the lymph nodes draining the injection site. In one animal, the administered BCG strain was recovered from the mediastinal lymph nodes. Interferon gamma (IFN-) release assay showed that VPM1002 and NUOG induced a strong antigen-specific response comparable to that elicited by BCG, while the response to PDX was delayed. Flow cytometry analysis of IFN- production by CD4+, CD8+, and T cells showed that CD4+ T cells of VPM1002- and NUOG-vaccinated goats produced more IFN- compared to BCG-vaccinated and mock-treated animals. In summary, the subcutaneous application of VPM1002 and NUOG induced anti-tuberculous immunity, while exhibiting a comparable safety profile to BCG in goats. dc:creator: Julia Figl, Heike Köhler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann and Christian Menge dcterms:created: 2023-03-14T04:32:08Z Last-Modified: 2023-03-14T04:38:41Z dcterms:modified: 2023-03-14T04:38:41Z dc:format: application/pdf; version=1.7 title: Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model Last-Save-Date: 2023-03-14T04:38:41Z pdf:docinfo:creator_tool: LaTeX with hyperref access_permission:fill_in_form: true pdf:docinfo:keywords: VPM1002; Bacille Calmette-Guérin; immune response; tuberculosis vaccine; goat model pdf:docinfo:modified: 2023-03-14T04:38:41Z meta:save-date: 2023-03-14T04:38:41Z pdf:encrypted: false dc:title: Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model modified: 2023-03-14T04:38:41Z cp:subject: A more effective vaccine against tuberculosis than Bacille Calmette-Guérin (BCG) is urgently needed. BCG derived recombinant VPM1002 has been found to be more efficacious and safer than the parental strain in mice models. Newer candidates, such as VPM1002 pdx1 (PDX) and VPM1002 nuoG (NUOG), were generated to further improve the safety profile or efficacy of the vaccine. Herein, we assessed the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, in juvenile goats. Vaccination did not affect the goats? health in regards to clinical/hematological features. However, all three tested vaccine candidates and BCG induced granulomas at the site of injection, with some of the nodules developing ulcerations approximately one month post-vaccination. Viable vaccine strains were cultured from the injection site wounds in a few NUOG- and PDX- vaccinated animals. At necropsy (127 days post-vaccination), BCG, VPM1002, and NUOG, but not PDX, still persisted at the injection granulomas. All strains, apart from NUOG, induced granuloma formation only in the lymph nodes draining the injection site. In one animal, the administered BCG strain was recovered from the mediastinal lymph nodes. Interferon gamma (IFN-) release assay showed that VPM1002 and NUOG induced a strong antigen-specific response comparable to that elicited by BCG, while the response to PDX was delayed. Flow cytometry analysis of IFN- production by CD4+, CD8+, and T cells showed that CD4+ T cells of VPM1002- and NUOG-vaccinated goats produced more IFN- compared to BCG-vaccinated and mock-treated animals. In summary, the subcutaneous application of VPM1002 and NUOG induced anti-tuberculous immunity, while exhibiting a comparable safety profile to BCG in goats. pdf:docinfo:subject: A more effective vaccine against tuberculosis than Bacille Calmette-Guérin (BCG) is urgently needed. BCG derived recombinant VPM1002 has been found to be more efficacious and safer than the parental strain in mice models. Newer candidates, such as VPM1002 pdx1 (PDX) and VPM1002 nuoG (NUOG), were generated to further improve the safety profile or efficacy of the vaccine. Herein, we assessed the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, in juvenile goats. Vaccination did not affect the goats? health in regards to clinical/hematological features. However, all three tested vaccine candidates and BCG induced granulomas at the site of injection, with some of the nodules developing ulcerations approximately one month post-vaccination. Viable vaccine strains were cultured from the injection site wounds in a few NUOG- and PDX- vaccinated animals. At necropsy (127 days post-vaccination), BCG, VPM1002, and NUOG, but not PDX, still persisted at the injection granulomas. All strains, apart from NUOG, induced granuloma formation only in the lymph nodes draining the injection site. In one animal, the administered BCG strain was recovered from the mediastinal lymph nodes. Interferon gamma (IFN-) release assay showed that VPM1002 and NUOG induced a strong antigen-specific response comparable to that elicited by BCG, while the response to PDX was delayed. Flow cytometry analysis of IFN- production by CD4+, CD8+, and T cells showed that CD4+ T cells of VPM1002- and NUOG-vaccinated goats produced more IFN- compared to BCG-vaccinated and mock-treated animals. In summary, the subcutaneous application of VPM1002 and NUOG induced anti-tuberculous immunity, while exhibiting a comparable safety profile to BCG in goats. Content-Type: application/pdf pdf:docinfo:creator: Julia Figl, Heike Köhler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann and Christian Menge X-Parsed-By: org.apache.tika.parser.DefaultParser creator: Julia Figl, Heike Köhler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann and Christian Menge meta:author: Julia Figl, Heike Köhler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann and Christian Menge dc:subject: VPM1002; Bacille Calmette-Guérin; immune response; tuberculosis vaccine; goat model meta:creation-date: 2023-03-14T04:32:08Z created: 2023-03-14T04:32:08Z access_permission:extract_for_accessibility: true access_permission:assemble_document: true xmpTPg:NPages: 25 Creation-Date: 2023-03-14T04:32:08Z pdf:charsPerPage: 3788 access_permission:extract_content: true access_permission:can_print: true meta:keyword: VPM1002; Bacille Calmette-Guérin; immune response; tuberculosis vaccine; goat model Author: Julia Figl, Heike Köhler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann and Christian Menge producer: pdfTeX-1.40.21 access_permission:can_modify: true pdf:docinfo:producer: pdfTeX-1.40.21 pdf:docinfo:created: 2023-03-14T04:32:08Z