An ideal vaccine antigen should elicit a strong immune response, provide broad protection against mutated pathogens, and ensure safety. Designing an antigen satisfying most of these criteria remains one of the biggest hurdles in vaccine development.
The GDT tool is unique in its ability to assess evolutionary conservativeness of peptides of any length and the ability to analyze insertion and deletion on top of substitution mutations. Additionally, immune response prediction tools can help identify T-cell/B-cell activation potential and individual HLA subtype compatibility.
With these innovations, BethBio enables the development of broadly reactive vaccines, therapeutic vaccines, and even personalized immunotherapies tailored to individual immune systems.
An ideal vaccine antigen should have the following properties. Firstly, the antigen should be able to elicit a strong, robust and specific response that allows the immune system to eliminate the pathogen or protect the host from infection. This requires the epitopes on the antigen to be recognizable by the immune system and can efficiently activate the T-cell or B-cell pathways in a way that triggers the desired immune response.
In addition to antigenicity, ideally, antigens should also be able to generate broad protection against a family of related, mutated pathogens. This is because some pathogens can evolve rapidly under selective pressures and can quickly mutate their antigens to evade immune detection. This can render a vaccine ineffective and cause a pipeline to fail at later stages, even if the products performed well in the early clinical stage. To counteract this, the ideal antigen should include epitopes targeting conserved yet essential regions of the pathogen which are critical to its survival and difficult to mutate. This would allow the vaccine to offer broad and long-lasting protection against a wide range of pathogen variants.
An ideal antigen should also be stable, safe and will not trigger unwanted immune responses, side effects or toxicity. Not only because vaccines are generally purposed for mass administration which safety is paramount, it is also a key criterion to passing clinical trials. A successful vaccine product typically contains antigens that fulfill two out of the three ideal qualities. Conversely, the inability to identify antigens with sufficient ideal properties remains one of the biggest hurdles in developing new vaccine candidates.
To help vaccine developers identify and design effective antigens, BethBio is developing a series of novel bioinformatics tools that could be used independently or to complement conventional biological and immunological methods.
One of the technologies is the GDT, an advanced bioinformatics tool that can evaluate the evolutionary rate of individual epitopes. The tool allows vaccine producers to more reliably and efficiently identify stable and conservative epitopes that are resistant to mutations. Unlike other available methods in which the minimum unit for analyses must be a complete sequence or protein, GDT can evaluate genome sequences and peptides of any length, making it the only applicable method for assessing epitopes. Additionally, while conventional phylogenetic methods can only analyze substitution mutations due to methodology limitations, GDT is the only tool capable of analyzing insertion and deletion mutations, making it far more versatile and applicable for screening proteins, peptides, or epitope libraries from a wide range of pathogens.
To assist the identification of epitopes that generate effective immune responses, BethBio is also developing novel analytics to predict and characterize the immune properties of epitopes. The new analytics predict whether epitopes will generate T-cell or B-cell response, their corresponding HLA subtypes and how different immune systems might respond to the antigen. These analyses are also based on bioinformatics and mainly pathogen genomic data. They can be used independently or complement other molecular docking or immunological assays. Early studies have shown promising results, demonstrating potential in this field where high-quality immunological data is scarce.
With these novel bioinformatics technologies, BethBio is unlocking new possibilities of a wide range of novel vaccine products. For instance, by combining GDT with virus evolution prediction, BethBio can potentially design antigens for vaccines such as influenza that remain effective for multiple years, even against evolving strains. Identifying effective T-cell epitopes can also enable or accelerate the development of therapeutic vaccines targeting chronic infections or diseases like cancer.
In addition, besides circulating viruses, cancer cells often also have unstable genomes and mutate drastically, which is a major impediment in identifying consistent neoantigens. The ability to identify genetically stable epitopes with GDT can significantly improve chances of developing long-lasting therapeutic cancer vaccines, antivirals, and monoclonal antibodies. Meanwhile, T-cell and HLA predictions will also support the design of individualized neoantigens tailored to patients’ unique immune systems, paving the way for personalized immunotherapies.
All of BethBio’s solutions can be integrated with additional analytical tools, such as protein structure modeling and experimental databases, to provide vaccine developers with a comprehensive platform for identifying ideal epitopes and designing novel vaccine products.
BethBio's bioinformatics technologies, including the GDT and immune response predictions, offer unmatched capabilities that set them apart from other available solutions. Whether you are working on infectious diseases, therapeutic vaccines, or cancer immunotherapies, our tools are designed to empower your research and development. Contact us today at business@bethbio.com to discover how our innovative solutions can enhance your vaccine development pipeline and help you design novel, effective, and longer-lasting products.