Tuberculosis, Journal Year: 2024, Volume and Issue: 148, P. 102537 - 102537
Published: June 27, 2024
Interferon-gamma release assay (IGRA) for tuberculosis (TB) remains limited in its ability to discriminate between active TB (ATB) and latent infection (LTBI). Activation markers on host T NK cells are currently considered be promising the diagnosis of ATB.
Language: Английский
Small, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 5, 2025
Abstract After more than a century since its initial development, Bacille Calmette‐Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated recombinant proteins, here we developed novel modular peptide‐based platform that is flexible, cold‐chain independent and customizable diverse circumstances populations. Each individual peptide building block consists of linear arrangement comprising 15‐leucine self‐assembly inducer moiety, Mycobacterium (Mtb) target epitope an human leukocyte antigen E (HLA‐E) binding with each moiety separated by triple lysine spacer. The blocks, any combination, able form multiepitope nanoparticle. Six Mtb epitopes were selected produce self‐assembling self‐adjuvating TB nano‐vaccine candidate PNx6. In vivo vaccination‐challenge experiments demonstrated subcutaneous boost parenteral immunization PNx6 significantly enhanced immunogenicity improved protective efficacy murine model 5‐fold. This study presents evidence purely amphiphilic peptides self‐assemble into nanoparticles appropriate size morphology for vaccination great potential multitude other diseases.
Language: Английский
Citations
2
Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 7, 2025
Mycobacterium tuberculosis (Mtb) is the pathogenic agent of (TB). Intracellular survival plays a central role in pathogenesis Mtb manner that dependent on an array transcriptional regulators for Mtb. However, functionality JTY_0672, member TetR family regulators, remains unknown. In this study, EMSA, BIL, ChlP-PCR and animal models were used to investigate regulation function protein. We found regulator JTY_0672 broad-spectrum regulatory protein can directly regulate JTY_3148, both vitro vivo. Cofactors containing V B1, B3, B6, C , His, Cys, Asp, Glu, Fe3+, Pb2+, Cu2+, Li+ inhibit binding between promoter JTY_3148. enhanced TAG production increased Isoniazid (INH) resistance. Besides, either promoted recalcitrance host immune response induced pathological injury inflammation. summary, research identified new targets cofactors deciphered physiological JTY_0672. Our findings will provide important theoretical basis understanding mechanism.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 5, 2024
Abstract After more than a century since its initial development, Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). Subunit boosters are considered viable strategy to enhance BCG efficacy, which often wanes in adolescence. While many studies on booster subunit vaccines have concentrated recombinant proteins, here we developed novel modular peptide-based platform that is flexible, cold-chain independent and customizable diverse circumstances populations. Each individual peptide building block consists of linear arrangement comprising 15-leucine self-assembly inducer moiety, Mycobacterium (Mtb) target epitope an HLA-E binding with each moiety separated by triple lysine spacer. The blocks, any combination, were able form multiepitope nanoparticle. Six Mtb epitopes selected produce self-assembling self-adjuvanting TB nano-vaccine candidate PNx6. In vivo vaccination-challenge experiments demonstrated subcutaneous boost parenteral immunization PNx6 significantly enhanced immunogenicity improved protective efficacy murine model 5-fold. Our study present evidence purely amphiphilic peptides self-assemble into nanoparticles appropriate size morphology for vaccination great potential multitude other diseases.
Language: Английский
Citations
1
Tuberculosis, Journal Year: 2024, Volume and Issue: 148, P. 102537 - 102537
Published: June 27, 2024
Interferon-gamma release assay (IGRA) for tuberculosis (TB) remains limited in its ability to discriminate between active TB (ATB) and latent infection (LTBI). Activation markers on host T NK cells are currently considered be promising the diagnosis of ATB.
Language: Английский
Citations
0