{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:46:13Z","timestamp":1791233173236,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Ministry for Education and Research (BMBF)","award":["03ZZ0806C"],"award-info":[{"award-number":["03ZZ0806C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A more effective vaccine against tuberculosis than Bacille Calmette-Gu\u00e9rin (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 \u0394pdx1 (PDX) and VPM1002 \u0394nuoG (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\u2019 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-\u03b3) 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-\u03b3 production by CD4+, CD8+, and \u03b3\u03b4 T cells showed that CD4+ T cells of VPM1002- and NUOG-vaccinated goats produced more IFN-\u03b3 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.<\/jats:p>","DOI":"10.3390\/ijms24065509","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:29:16Z","timestamp":1678764556000},"page":"5509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safety and Immunogenicity of Recombinant Bacille Calmette-Gu\u00e9rin Strain VPM1002 and Its Derivatives in a Goat Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Julia","family":"Figl","sequence":"first","affiliation":[{"name":"Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Wedlich","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"Liebler-Tenorio","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leander","family":"Grode","sequence":"additional","affiliation":[{"name":"Vakzine Projekt Management GmbH, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Parzmair","sequence":"additional","affiliation":[{"name":"Vakzine Projekt Management GmbH, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopinath","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5749-2462","authenticated-orcid":false,"given":"Natalie E.","family":"Nieuwenhuizen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-8268","authenticated-orcid":false,"given":"Stefan H. E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany"},{"name":"Max Planck Institute for Multidisciplinary Sciences, 37077 G\u00f6ttingen, Germany"},{"name":"Hagler Institute for Advanced Study, Texas A&M University, College Station, TX 7843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Menge","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). 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