Involucrin-driven Retroviral Expression Cassettes Encoding Human Immunodeficiency Virus Envelope Glycoproteins

Description

Infectious diseases are a leading cause of mortality worldwide, resulting in more than 17 million deaths each year. Infections are caused by organisms, such as bacteria, viruses, fungi, or parasites, passed directly or indirectly from one person to another. The most viable method for prevention against many infectious diseases is through vaccination. Vaccines introduce an inactive form of the pathogen to the body, enabling the development of immunity and protection from the infectious agent. Although effective vaccines have been FDA approved for many infections, there are many pathogens for which vaccines do not exist. The lack of vaccines is primarily due to challenges in development for sufficiently presenting viral proteins to the body’s immune system to elicit immunity.

An inventor at Texas Biomed has developed a novel vaccine platform for HIV and other infectious diseases for which there are no effective vaccines. The inventor utilizes epithelial stem cells (ESCs) as a permanent source of antigens specific for pathogens, including but not limited to HIV. This strategy uses the host ESCs as mucosal adjuvant to “carry” specific antigen and keep the immune response in alert at the infection site. It uses a promoter called Involucrin to force ESCs to continuously express viral antigens that are not eliminated by the body’s immune system. The vaccine remains in ESCs with its expression limited to only this lineage, which naturally matures and senesces. The vaccine has been reduced to practice through several preclinical studies and tested for safety and efficacy in a viral challenge study in monkeys using Simian immunodeficiency virus (SIV). Monkeys that received the vaccine delivered mucosally exhibited a significant delay in viral transmission, positive correlations in T cell responses, and durable protection and control of infection for up to three years compared to placebo.

Benefits and Advantages

• Novel vaccine platform that uses ESCs to continuously present viral proteins to the body’s immune system.
• Late-stage preclinical studies show the vaccine stimulates the immune system to specifically target viruses and block viral entry.
• Provides long-lasting protection against and control of infection by SIV for up to three years after vaccination.
• The platform technology can be used to develop vaccines for a wide variety of pathogens, including those with no FDA-approved agent like HIV/AIDS, COVID-19/SARS, Zika, Influenza, Malaria, Dengue, Chagas, and Respiratory Syncytial Virus (RSV).
• A novel, single-dose vaccine platform that can be administered mucosally, which could potentially be adapted to neonates and infants.

MARIE-CLAIRE GAUDUIN, Ph.D.

Associate Professor

Dr. Gauduin has more than 25 years of experience in HIV/AIDS research and medical microbiology. She has been working extensively on HIV, TB, and the development of novel vaccine strategies using the nonhuman primate model for infectious disease. Dr. Gauduin has also developed a neonatal model for tuberculosis to study HIV/TB co-infection in pediatric AIDS.

Inside The Lab

SIV transmission. Our lab is investigating the early events of SIV transmission in macaques using a recombinant SIV tagged with a green fluorescent protein (GFP) as a sensitive tool to monitor infected cells in vivo.

This construct allows us to identify the:

1. Initial infected cells, their phenotype and function
2. Mechanisms, time course, and routes of viral spread from the site of initial infection to lymphoid organs and blood
3. Generation of early SIV-specific immune response from the mucosal site of Infection.

These factors are critical for the development of effective vaccines.

HIV vaccine design and development. One key obstacle to an effective AIDS vaccine has been the inability to deliver antigen for a sufficient period of time. Because HIV transmission occurs mainly across mucosal surfaces, the ideal vaccine strategy would be to target HIV at mucosal entry sites of transmission to prevent infection.

Maternal transmission of HIV-1 accounts for most cases of pediatric HIV-1 infection. Using a macaque model, we are investigating the early virus-specific T cell responses in neonatesorally infected with a pathogenic or nonpathogenic strain of SIV, (an HIV laboratory surrogate).

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 more than 75 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 (HPI) – 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, Flow Cytometry, 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, visit www.txbiomed.org. To learn more about partnering with our world-class researchers to execute quality scientific studies, please contact Applied Science and Innovation at