Engineered prefusion-stabilized RSV fusion proteins and nucleic acids for enhanced vaccines and diagnostics

This technology uses engineered RSV prefusion proteins with specific mutations to boost stability, expression, and shelf life, enabling more effective and affordable RSV vaccines, treatments, and diagnostics in both protein and nucleic acid (e.g., mRNA) formats.

Background

Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory illness worldwide, particularly affecting infants, young children, the elderly, and immunocompromised individuals. The virus is responsible for millions of hospitalizations and substantial mortality each year, making the development of effective vaccines and therapeutics a high public health priority. Central to RSV vaccine design is the fusion (F) protein, which facilitates viral entry into host cells. The prefusion conformation of the F protein is especially important because it presents unique epitopes that elicit potent neutralizing antibody responses, making it the preferred target for next-generation vaccines and monoclonal antibody therapies.

Despite advances in RSV vaccine development, significant challenges remain with current approaches. Existing prefusion-stabilized F protein antigens, while immunogenic, often suffer from low expression yields in mammalian cell culture, which increases production costs and limits scalability. Additionally, the prefusion form is inherently unstable and prone to converting into the less immunogenic post fusion state, reducing vaccine efficacy. Limited thermostability further complicates storage and distribution, particularly in regions lacking robust cold chain infrastructure. These technical hurdles hinder the widespread adoption and effectiveness of RSV vaccines and diagnostic tools, underscoring the need for improved antigen designs that address these persistent issues.

Technology description

This technology centers on engineered variants of the Respiratory Syncytial Virus (RSV) fusion (F) protein ectodomain, specifically designed to stabilize the prefusion conformation through targeted amino acid substitutions. These modifications—such as introducing disulfide bonds, optimizing hydrophobic packing, and incorporating proline substitutions—significantly enhance both the expression yield and thermostability of the protein when produced in mammalian cells. Stabilized F proteins are typically fused to trimerization domains, ensuring robust trimer formation, and can be produced either as recombinant proteins or encoded by nucleic acid molecules, including mRNA with chemical modifications for improved stability.

This platform supports a wide range of applications, including next-generation RSV vaccines (protein-based or nucleic acid-based), monoclonal antibody discovery, and diagnostic assays, by overcoming the historical challenges of low yield and instability associated with previous RSV F protein antigens.

What differentiates this technology is its comprehensive approach to solving multiple longstanding issues in RSV vaccine development. Unlike earlier stabilized RSV F proteins, these engineered variants employ a novel combination of rationally designed mutations that not only lock the protein in its highly immunogenic prefusion state but also dramatically improve manufacturability and shelf life. The increased thermostability allows for easier storage and distribution, particularly in resource-limited settings where cold chain logistics are problematic.

Additionally, the preservation of critical neutralizing epitopes ensures potent immune responses, while the versatility of the platform supports deployment across various vaccine modalities, including protein subunit, mRNA, DNA, and nanoparticle-based vaccines. This broad utility, combined with superior expression yields and unique intellectual property, positions the technology as a significant advancement for RSV prevention, treatment, and diagnostics.

Technologies

Antibodies and antigens
Cell cultures
Genetically modified cells
Immunoassays
Peptides
Recombinant DNA
Testing biological material
Viruses and vectors

Benefits

Significantly enhanced protein expression yields in mammalian cells, reducing production costs and improving manufacturing scalability
Improved thermostability of the prefusion RSV F protein, extending shelf life and simplifying cold chain requirements
Preserved immunogenicity with potent neutralizing antibody responses targeting key prefusion epitopes
Versatile platform compatible with multiple vaccine modalities including protein-based, mRNA, DNA, and nanoparticle vaccines
Novel stabilizing mutations enabling superior stability and expression compared to existing RSV F protein antigens
Broad applicability in vaccine development, therapeutic antibody discovery, and diagnostic assay design
Facilitates production of stable trimeric prefusion RSV F proteins through fusion to trimerization domains

Commercial applications

Next-generation RSV protein vaccines
mRNA-based RSV vaccines
RSV diagnostic assay development
Monoclonal antibody discovery platforms

Opportunity

The University of Texas at Austin is seeking a commercial partner to license this patent. These are engineered variants of the Respiratory Syncytial Virus (RSV) fusion protein ectodomain. They are designed with specific amino acid substitutions, including disulfide bonds, to stabilize the prefusion conformation. This design significantly enhances protein expression and thermostability. These stabilized proteins are utilized in next-generation RSV vaccines, monoclonal antibody discovery, and diagnostic assays.