BCGΔBCG1419c
Candidate Overview
This is a second-generation version of BCGΔBCG1419c, devoid of antibiotic markers. It is based on BCG Pasteur ATCC 35734.
Sponsor / Lead Developer: Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco, A.C. (CIATEJ)
Primary Indication: Prevention of TB disease
Other Indication(s): Prevention of Mtb infection or sustained infection
Target Population(s): Adolescents, Adults, Children, Infants, People living with HIV, People with Mtb infection, and People without Mtb infection
Immune tissue localization: Lung, Lymph node, and Spleen
Immunological responses: B-cell/Antibody and T-cell
Preclinical Animal Models: Guinea pig and Mouse
Intended to elicit trained immunity: Yes
Additional Immunologic Response Information
HYPOTHESIZED | DEMONSTRATED |
|
| Immune Response | T-cell B-cell/antibody |
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| Characteristics of B-cell/antibody response | Promote the induction of antibodies targeting antigens not produced by "standard" BCG | Increased anti-PPD antibody titers in guinea pigs compared with those elicited by parental BCG |
| T-cell phenotype | Gamma-delta (γδ) Natural Killer (NK) CD1 | CD4 CD8 |
| T-cell functional profile | Polycytotoxicity Cytolytic Capacity | IFN-γ TNF-α |
| Preferential immune tissue localization | Lung Lymph node Spleen |
|
| Trained immunity | Yes |
Related Publications
- Proteome and immunogenicity differences in BCG Pasteur ATCC 35734 and its derivative, the vaccine candidate BCGΔBCG1419c during planktonic growth in 7H9 and Proskauer Beck media. (Tuberculosis (Edinburgh), 2024).
- BCG∆BCG1419c and BCG differ in induction of autophagy, c-di-GMP content, proteome, and progression of lung pathology in Mycobacterium tuberculosis HN878-infected male BALB/c mice. (Vaccine, 2023)
- Genome sequences of BCG Pasteur ATCC 35734 and its derivative, the vaccine candidate BCGΔBCG1419c. (BMC Genomics, 2023)
- BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis. (Sci Rep., 2022)
- Proteomic characterization of a second-generation version of the BCGΔBCG1419c vaccine candidate by means of electrospray-ionization quadrupole time-of-flight mass spectrometry. (Pathogens and Disease, 2020)
Additional Information
As mentioned above, the information and the links provided are those obtained after evaluation of the second-generation version of BCGΔBCG1419c, devoid of antibiotic markers. It is based on BCG Pasteur ATCC 35734. We have additionally published experimental preclinical data for the first-generation, hygromycin-resistant version, based on BCG Pasteur 1173P2. Those results include:
Flores-Valdez MA, Aceves-Sánchez M de J, Pedroza-Roldán C, Vega-Domínguez PJ, Prado-Montes de Oca E, Bravo-Madrigal J, Laval F, Daffé M, Koestler B, Waters CM. The Cyclic Di-GMP Phosphodiesterase Gene Rv1357c/BCG1419c Affects BCG Pellicle Production and In Vivo Maintenance. IUBMB Life. 2015 Feb;67(2):129-38. doi: 10.1002/iub.1353.
Pedroza-Roldán C, Guapillo C, Barrios-Payán J, Mata-Espinosa D, Aceves-Sánchez MJ, Marquina-Castillo B, Hernández-Pando R, Flores-Valdez MA. The BCGΔBCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo. Vaccine. 34 (2016) 4763-4770. pii: S0264-410X(16)30707-1. doi: 10.1016/j.vaccine.2016.08.035.
Parasa VR, Rose J, Castillo-Diaz LA, Aceves-Sánchez MJ, Vega-Domínguez PJ, Lerm M, Flores-Valdez MA. Evaluation of the immunogenic capability of the BCG strains BCGΔBCG1419c and BCGΔBCG1416c in a three-dimensional human lung tissue model. Vaccine. 2018 Mar 27;36(14):1811-1815. doi: 10.1016/j.vaccine.2018.02.044.
Segura-Cerda CA, Aceves-Sánchez MJ, Marquina-Castillo B, Mata-Espinoza D, Barrios-Payán J, Vega-Domínguez PJ, Pedroza-Roldán C, Bravo-Madrigal J, Vallejo-Cardona AA, Hernández-Pando R, Flores-Valdez MA. Immune response elicited by two rBCG strains devoid of genes involved in c-di-GMP metabolism affect protection versus challenge with M. tuberculosis strains of different virulence. Vaccine. 2018 Apr 12;36(16):2069-2078. https://doi.org/10.1016/j.vaccine.2018.03.014.
Flores-Valdez MA, Pedroza-Roldán C, Aceves-Sánchez MdJ, Peterson EJR, Baliga NS, Hernández-Pando R, Troudt J, Creissen E, Izzo L, Bielefeldt-Ohmann H, Bickett T and Izzo AA (2018) The BCGΔBCG1419c Vaccine Candidate Reduces Lung Pathology, IL-6, TNF-α, and IL-10 During Chronic TB Infection. Front Microbiol. 2018 Jun 12;9:1281. https://doi.org/10.3389/fmicb.2018.01281.
Sathkumara H, Pai S, Aceves-Sánchez MJ, Ketheesan N, Flores-Valdez MA and Kupz A. BCG Vaccination Prevents Reactivation of Latent Lymphatic Murine Tuberculosis Independently of CD4+ T Cells. Front. Immunol. 10:532. doi: 10.3389/fimmu.2019.00532.
Segura-Cerda, C.A., Marquina-Castillo, B., Lozano-Ordaz, V. Mata-Espinosa, D., Barrios-Payán, J.A., López-Torres, M.O., Aceves-Sánchez, M.J., Bielefeldt-Ohmann, H., Hernández-Pando, R., & Flores-Valdez, M.A. BCG and BCGΔBCG1419c protect type 2 diabetic mice against tuberculosis via different participation of T and B lymphocytes, dendritic cells and pro-inflammatory cytokines. npj Vaccines 5, 21 (2020). https://doi.org/10.1038/s41541-020-0169-6.
Gunasena, M., Shukla, R.K., Yao, Rosas-Mejia, O., Powell, M.D., Oestrich, K.J., Aceves-Sánchez, M.J., Flores-Valdez, M.A., Liyanage, N.P., and Robinson, R.T. Evaluation of early innate and adaptive immune responses to the TB vaccine Mycobacterium bovis BCG and vaccine candidate BCGΔBCG1419c. Sci Rep 12, 12377 (2022). https://doi.org/10.1038/s41598-022-14935-y