Development of Novel, Next-Generation, Double and Triple Knock-out (DKO, TKO) Vaccines Effective Against Tuberculosis Based on sigH

Description

Nine new deletion strains of Mycobacterium tuberculosis (Mtb), the bacterium responsible for tuberculosis (TB), have been developed. Mtb is a leading cause of infectious disease-related deaths globally. Each of these strains includes a complete deletion of the sigH gene (LlsigH), which encodes a transcription factor that helps Mtb survive stress from immune cells in the lungs, allowing it to cause disease. The deletion of sigH renders the bacteria non-pathogenic (unable to cause disease) while also providing protection against future Mtb infections.

Market Need

There is a significant market need for new tuberculosis (TB) prevention technologies, as the disease remains one of the leading causes of death worldwide, particularly in low- and middle-income countries. Existing TB vaccines, such as the BCG vaccine, offer limited and inconsistent protection, especially in adults. The rise of drug-resistant strains of Mycobacterium tuberculosis (Mtb) further complicates treatment efforts, making the development of more effective vaccines critical. With over 10 million new TB cases reported annually and increasing global attention on infectious diseases, there is an urgent demand for advanced vaccines that can provide stronger, long-lasting protection. The technology behind multi-gene deletion strains of Mtb, which are non-pathogenic and protective, has the potential to fill this gap, offering a novel and safer approach to TB prevention and addressing the shortcomings of current vaccine options.

Benefits and Advantages

  • Enhanced Safety: The deletion of key genes ensures the modified Mycobacterium tuberculosis strains are non-pathogenic, making them safer for vaccine use
  • Stronger Protection: These Strains offer longer-lasting and more effective immunity against future Mtb infections compared to current vaccines.
  • Regulatory Compatibility: The multi-gene deletions meet international safety standards for TB Vaccines, enabling smoother progression to human trials

Deepak Kaushal, Ph.D.

Professor

Dr Deepak Kaushal is a professor at Texas Biomedical Research Institute (Texas Biomed). He is recognized for having developed the macaque model of TB using the natural inhaltion route of infection and a model of Mtb/HIV co-infection

Deepak Kaushal

Inside The Lab

Dr. Kaushal and his team have made significant breakthroughs in understanding how Mycobacterium tuberculosis (Mtb) interacts with primate lungs, especially within granulomas. Their research has provided key insights into both the pathogen and the host’s environment. Using a macaque model for inhalation tuberculosis {TB) and TB/AIDS, they have created a platform to test new vaccines and treatments against TB.

Their research covers multiple aspects of Mtb infections, with a focus on the nonhuman primate model to study the natural infection process.

This model helps them understand how Mtb responds to stress in the body, the role of certain immune tissues in protecting against TB, and the identification of specific T cell responses that differentiate between protection and disease progression. They also study mechanisms of TB protection that do not rely on CD4 T cells and how HIV reactivates TB.

Additionally, Dr. Kaushal’s lab is working to identify biomarkers for different stages of TB infection and disease. They are exploring host-directed treatments for TB, focusing on approaches that target the host’s immune response rather than just the pathogen itself. One of their goals is to develop a highly safe, stress-response-based attenuated TB vaccine.

Texas Biomedical Research Institute pioneers and shares scientific breakthroughs that protect you, your families, and our global community from the threat of infectious diseases. Texas Biomed is an independent, not-for-profit, research institute with a strong history of collaborating with global partners and contributing to the world of science and human health for nearly 80 years. We are evolving into a one-of-a-kind, world-leader in the broad sciences of infectious diseases, with researchers working together in three critical areas of discovery. Our partnerships continue to expand globally to deliver new diagnostics, treatments and cures through our pre-clinical research and development programs.

Scientific Programs

Host-Pathogen Interactions {HP/) – The HPI Program concentrates on the basic biology of infection in humans and animals and the development of disease.

Disease Intervention & Prevention {DIP} – The DIP Program aids in the development of diagnostics, treatments, and vaccines to prevent disease, reduce severity of disease and infection, if not cure infection.

Population Health {PH) – The PH program aims to identify correlates of disease susceptibility or resistance to infectious diseases on a population level.

Resource Attributes

BSL-3 and BSL-4 facilities with laboratory capacity to perform in vitro experiments (biochemistry, cell biology, molecular genetics, and immunology) and in vivo studies (vaccine/therapeutic efficacy, pathogenesis, and survival) including imaging.

Experience with the development of nonhuman primate (baboon, macaque, marmoset)  and rodent (mouse, hamster, and guinea pig) models for evaluating disease pathology and diagnostic, therapeutic or vaccine efficacy.

Established standard operating procedures and protocols for biochemical, immunological and metabolism assays, deep sequencing, neutralization assays, determining bacterial and viral load among others.

Facilities equipped with state-of-the-art equipment including Aerobiology instrumentation, Telemetry, Clinical Pathology Instrumentation,FlowCytometry,Sorting, PET-CT scan, Live-Imaging, and Single-Cell Sequencing among others.

Active programs with NIH/DOD/BARDA/MCS, commercial and international partners.Studies adhering to robust quality standards to support regulatory filings with the FDA and other agencies.

For more information on Texas Biomed’s Applied Science and Innovation, please visit our Web page. To learn more about partnering with our world-class faculty and researchers on quality scientific studies, please contact Business Development and Strategic Alliances, Applied Science and Innovation, Texas Biomedical Research Institute, San Antonio at