This technology uses engineered hantavirus glycoproteins stabilized in their prefusion form to create more effective vaccines, antibody therapies, and diagnostic tools, improving immune response, production efficiency, and shelf life for hantavirus prevention and detection.
Background
Hantaviruses are a group of zoonotic viruses that cause severe and often fatal diseases in humans, such as hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). These diseases are characterized by high mortality rates and limited treatment options, making prevention through vaccination a critical public health goal. The viral surface glycoproteins, Gn and Gc, play a central role in viral entry into host cells and are the primary targets for neutralizing antibodies generated by the immune system. However, despite the urgent need for effective vaccines and diagnostic tools, there are currently no licensed protein subunit vaccines for hantaviruses, and existing approaches—such as inactivated or DNA vaccines—have shown limited efficacy or face significant manufacturing and distribution challenges.
Current vaccine and diagnostic development efforts are hampered by several technical obstacles. The native hantavirus glycoprotein complex exists as a tetramer in a specific prefusion conformation on the viral surface, which is essential for exposing key neutralizing epitopes. However, when these glycoproteins are produced recombinantly for research or vaccine purposes, they tend to dissociate into monomers or adopt post-fusion conformations, both of which lack the critical structural features necessary to elicit strong, protective immune responses. Additionally, these recombinant proteins are often unstable, difficult to express at high yields, and prone to degradation, resulting in increased production costs and reduced shelf life. These limitations not only hinder the development of effective vaccines but also restrict the availability of reliable antigens for monoclonal antibody discovery and diagnostic assays, leaving a significant gap in the ability to prevent and control hantavirus outbreaks.
Technology Description
This technology centers on engineered hantavirus glycoprotein complexes, specifically the Gn and Gc proteins from the Andes virus, which have been modified through targeted amino acid substitutions and the incorporation of a designed motif to stabilize their tetrameric glycoprotein in the prefusion conformation. By maintaining this native-like structure, the engineered complexes preserve critical neutralizing epitopes that are often lost in monomeric or post-fusion forms, thereby enhancing their ability to elicit strong and protective immune responses. The stabilized glycoproteins exhibit improved recombinant expression, increased solubility, and enhanced thermostability, resulting in lower production costs and extended shelf life. These features make the complexes highly versatile, serving as antigens for protein-based or mRNA-based vaccines, tools for monoclonal antibody discovery, and components in diagnostic assays for hantavirus-specific immune responses. The technology is adaptable to other pathogenic hantaviruses by tailoring the stabilizing substitutions and motifs.
What differentiates this technology is its ability to closely mimic the native tetrameric structure of hantavirus surface glycoproteins, a feature critical for effective immune recognition and neutralization. Unlike previous approaches, which often rely on DNA or inactivated vaccines and lack protein subunit options, this solution is the first to provide a soluble, prefusion-stabilized tetrameric hantavirus glycoprotein complex. The structural integrity is validated by high-resolution cryo-EM, revealing detailed molecular interfaces and pH-sensing mechanisms that are essential for viral entry and immune targeting. The inclusion of engineered motifs and specific amino acid changes not only stabilizes the prefusion state but also enables efficient production and formulation as either recombinant proteins or nucleic acids (including mRNA and self-replicating RNA), with demonstrated immunogenicity in animal models. This comprehensive design makes the technology broadly applicable, highly manufacturable, and well-suited for next-generation vaccines, therapeutics, and diagnostics targeting hantaviruses.
Benefits
Commercial applications
Additional information
These engineered hantavirus Gn and Gc glycoproteins, modified via specific amino acid substitutions and a designed motif, stabilize the viral tetrameric spike in its prefusion conformation. This preserves neutralizing epitopes, enhancing protective immune responses. The complexes exhibit improved recombinant expression and thermostability, serving as antigens for vaccine formulations, tools for monoclonal antibody discovery, and components for diagnostic assays.
Publication
Intellectual Property
Provisional filed 07/29/2025
