Gene Therapy Platform for In Vivo Delivery and Expression of Protective Anti-Rabies Antibodies

Background

Rabies is a highly lethal viral disease that causes acute encephalitis in humans and animals, with nearly 100% fatality once clinical symptoms appear. The disease remains a significant public health concern, particularly in resource-limited regions where access to timely medical intervention is scarce. Traditional rabies prevention relies on post-exposure prophylaxis (PEP), which combines a series of vaccinations with administration of rabies immunoglobulin (RIG). However, the complexity of the vaccination schedule, the need for cold-chain storage, and the high cost of RIG limit the effectiveness and accessibility of current interventions, especially in rural and underserved populations. The persistence of rabies as a global health threat underscores the urgent need for more efficient, accessible, and long-lasting prophylactic and therapeutic solutions.

Current approaches to rabies prevention and treatment are fraught with logistical, immunological, and practical challenges. Vaccines require multiple doses over several weeks, which can be difficult to complete in areas with limited healthcare infrastructure or where follow-up is unreliable. Rabies immunoglobulin, essential for immediate passive immunity, is expensive, in short supply, and often unavailable in the regions where it is most needed. Moreover, both vaccines and RIG may be less effective in immunocompromised individuals or in those with pre-existing passive immunity, such as newborns with maternal antibodies. The need for repeated administration, ongoing titer monitoring, and the risk of adverse reactions further complicate rabies management. These limitations highlight the inadequacy of current strategies and the necessity for innovative approaches that can provide rapid, robust, and durable protection against rabies with fewer logistical hurdles.

Technology

This technology is a gene therapy platform designed to prevent and treat rabies lyssavirus infection, including rabies encephalitis, by using recombinant adeno-associated virus (AAV) vectors to deliver genetic instructions for producing anti-rabies immunoglobulins directly within the body. The core system employs engineered AAV vectors—such as pAAV-CBA-CR57-nHL-wpre—that encode both the heavy and light chains of potent anti-rabies antibodies, driven by robust regulatory elements like the CMV enhancer and chicken beta-actin promoter. Upon administration, these vectors are capable of crossing the blood-brain barrier and inducing the sustained production of functional antibodies in both the central nervous system and peripheral tissues. The platform supports a variety of antibody formats, including full-length monoclonal antibodies, fragments, and multispecific constructs, and can be administered through multiple routes (intravenous, intramuscular, subcutaneous, oral, or nasal), making it suitable for use in humans and animals alike.

What differentiates this technology is its ability to provide rapid, robust, and long-lasting protection against rabies after a single dose—an especially critical advantage given the rapid progression and near-universal fatality of untreated rabies. Unlike traditional vaccines, which require multiple doses and may be less effective in immunocompromised individuals or those with passive immunity, this gene therapy ensures high, durable antibody titers that exceed protective thresholds and are effective even in challenging clinical scenarios. The use of AAV vectors enables targeted delivery and expression in the CNS, a key site for rabies pathogenesis, and the modular design allows for adaptation to express multiple antibodies or to target other pathogens. This approach not only streamlines prophylaxis and post-exposure treatment but also addresses logistical and economic barriers, offering a transformative solution for rabies control, particularly in resource-limited settings.

Benefits

• Provides rapid and robust protective immunity against rabies after a single administration.
• Enables durable, potentially lifelong antibody expression reducing the need for booster vaccinations.
• Crosses the blood-brain barrier to deliver antibodies directly to the central nervous system.
• Effective in immunocompromised individuals and those with passive maternal immunity.
• Flexible antibody formats and vector designs allow broad protection against viral variants.
• Applicable to humans and various animal species, including companion animals and livestock.
• Reduces logistical challenges and costs associated with traditional rabies vaccination and immunoglobulin therapies.
• Supports multiple administration routes, enhancing accessibility and ease of use.

Applications

• Single-dose rabies post-exposure prophylaxis
• Long-term rabies prevention in animals
• Rapid rabies outbreak containment
• Rabies protection for immunocompromised patients

Additional info

This gene therapy employs recombinant adeno-associated virus (AAV) vectors to deliver genetic constructs for in vivo expression of anti-rabies immunoglobulins. Administered once, these vectors cross the blood-brain barrier, ensuring systemic and central nervous system antibody production that neutralizes rabies lyssavirus, providing rapid, durable protection.