Stage of Development

Preclinical Evaluation

Vaccine Platform

Mycobacterial – Live Attenuated

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

Immune ResponseT-cell
Characteristics of B-cell/antibody responsePromote the induction of antibodies targeting antigens not produced by "standard" BCGIncreased anti-PPD antibody titers in guinea pigs compared with those elicited by parental BCG
T-cell phenotypeGamma-delta (γδ)
Natural Killer (NK)
T-cell functional profilePolycytotoxicity
Cytolytic Capacity
Preferential immune tissue localizationLung
Lymph node
Trained immunityYes

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.

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.

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).

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).