Cargando…
Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model
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 Δpdx1 (PDX) and VPM1002 ΔnuoG (NUOG), were g...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058566/ https://www.ncbi.nlm.nih.gov/pubmed/36982586 http://dx.doi.org/10.3390/ijms24065509 |
_version_ | 1785016662312878080 |
---|---|
author | Figl, Julia Köhler, Heike Wedlich, Nadine Liebler-Tenorio, Elisabeth M. Grode, Leander Parzmair, Gerald Krishnamoorthy, Gopinath Nieuwenhuizen, Natalie E. Kaufmann, Stefan H. E. Menge, Christian |
author_facet | Figl, Julia Köhler, Heike Wedlich, Nadine Liebler-Tenorio, Elisabeth M. Grode, Leander Parzmair, Gerald Krishnamoorthy, Gopinath Nieuwenhuizen, Natalie E. Kaufmann, Stefan H. E. Menge, Christian |
author_sort | Figl, Julia |
collection | PubMed |
description | 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 Δpdx1 (PDX) and VPM1002 ΔnuoG (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-γ) 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-γ production by CD4(+), CD8(+), and γδ T cells showed that CD4(+) T cells of VPM1002- and NUOG-vaccinated goats produced more IFN-γ 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. |
format | Online Article Text |
id | pubmed-10058566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100585662023-03-30 Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model Figl, Julia Köhler, Heike Wedlich, Nadine Liebler-Tenorio, Elisabeth M. Grode, Leander Parzmair, Gerald Krishnamoorthy, Gopinath Nieuwenhuizen, Natalie E. Kaufmann, Stefan H. E. Menge, Christian Int J Mol Sci Article 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 Δpdx1 (PDX) and VPM1002 ΔnuoG (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-γ) 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-γ production by CD4(+), CD8(+), and γδ T cells showed that CD4(+) T cells of VPM1002- and NUOG-vaccinated goats produced more IFN-γ 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. MDPI 2023-03-14 /pmc/articles/PMC10058566/ /pubmed/36982586 http://dx.doi.org/10.3390/ijms24065509 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Figl, Julia Köhler, Heike Wedlich, Nadine Liebler-Tenorio, Elisabeth M. Grode, Leander Parzmair, Gerald Krishnamoorthy, Gopinath Nieuwenhuizen, Natalie E. Kaufmann, Stefan H. E. Menge, Christian Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model |
title | Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model |
title_full | Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model |
title_fullStr | Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model |
title_full_unstemmed | Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model |
title_short | Safety and Immunogenicity of Recombinant Bacille Calmette-Guérin Strain VPM1002 and Its Derivatives in a Goat Model |
title_sort | safety and immunogenicity of recombinant bacille calmette-guérin strain vpm1002 and its derivatives in a goat model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058566/ https://www.ncbi.nlm.nih.gov/pubmed/36982586 http://dx.doi.org/10.3390/ijms24065509 |
work_keys_str_mv | AT figljulia safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT kohlerheike safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT wedlichnadine safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT lieblertenorioelisabethm safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT grodeleander safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT parzmairgerald safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT krishnamoorthygopinath safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT nieuwenhuizennataliee safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT kaufmannstefanhe safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel AT mengechristian safetyandimmunogenicityofrecombinantbacillecalmetteguerinstrainvpm1002anditsderivativesinagoatmodel |