ArticleEBioMedicine2020
Live attenuated TB vaccines representing the three modern Mycobacterium tuberculosis lineages reveal that the Euro-American genetic background confers optimal vaccine potential.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 48 citations in OpenAlex.
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- Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution.Nature communications · 2024Article
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- Mouse Models forPathogens (Basel, Switzerland) · 2022Review
- Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis.Biomedicines · 2022Review
- BCGΔBCG1419c increased memory CD8Scientific reports · 2022Article
- TheInternational journal of molecular sciences · 2022Article
- TheMolecular therapy. Nucleic acids · 2022Article
- The MtZ Strain: Molecular Characteristics and Outbreak Investigation of the Most SuccessfulFrontiers in cellular and infection microbiology · 2022Article
- Pulmonary MTBVAC vaccination induces immune signatures previously correlated with prevention of tuberculosis infection.Cell reports. Medicine · 2021Article
- Engineering a new vaccine platform for heterologous antigen delivery in live-attenuatedComputational and structural biotechnology journal · 2021Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman tuberculosis (TB) is caused by a plethora of Mycobacterium tuberculosis complex (MTBC) strains belonging to seven phylogenetic branches. Lineages 2, 3 and 4 are considered "modern" branches of the MTBC responsible for the majority of worldwide TB. Since the current BCG vaccine confers variable protection against pulmonary TB, new candidates are investigated. MTBVAC is the unique live attenuated vaccine based on M. tuberculosis in human clinical trials.
methodsMTBVAC was originally constructed by unmarked phoP and fadD26 deletions in a clinical isolate belonging to L4. Here we construct new vaccines based on isogenic gene deletions in clinical isolates of the L2 and L3 modern lineages. These three vaccine candidates were characterized at molecular level and also in animal experiments of protection and safety.
findingsSafety studies in immunocompromised mice showed that MTBVAC-L2 was less attenuated than BCG Pasteur, while the original MTBVAC was found even more attenuated than BCG and MTBVAC-L3 showed an intermediate phenotype. The three MTBVAC candidates showed similar or superior protection compared to BCG in immunocompetent mice vaccinated with each MTBVAC candidate and challenged with three representative strains of the modern lineages.
interpretationMTBVAC vaccines, based on double phoP and fadD26 deletions, protect against TB independently of the phylogenetic linage used as template strain for their construction. Nevertheless, lineage L4 confers the best safety profile.
fundingEuropean Commission (TBVAC2020, H2020-PHC-643381), Spanish Ministry of Science (RTI2018-097625-B-I00), Instituto de Salud Carlos III (PI18/0336), Gobierno de Aragón/Fondo Social Europeo and the French National Research Council (ANR-10-LABX-62-IBEID, ANR-16-CE35-0009, ANR-16-CE15-0003).
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