Next-Generation Human Cytomegalovirus Glycoprotein B Vaccine Technology

This inventive concept envisions a next-generation human cytomegalovirus (HCMV) vaccine technology, leveraging strategically engineered disulfide mutations to enhance trimerization, stability, and immunogenicity of the glycoprotein B (gB) polypeptide, thereby providing broad protection against HCMV strains.

The original patent disclosed engineered mutants of the wild-type HCMV gB protein with improved stability in prefusion form. However, these mutants still had limitations in terms of trimerization efficiency, stability, and immunogenicity. The new inventive concept addresses these limitations by introducing novel disulfide mutations, optimized trimerization systems, and machine learning-based mutation prediction algorithms.

The next-generation HCMV vaccine technology comprises a recombinant vector system with a gB polypeptide harboring at least three strategically positioned engineered disulfide mutations. These mutations enhance trimerization and stability in prefusion form, resulting in improved immunogenicity. The inventive concept also includes a method for eliciting an immune response against HCMV, utilizing a vaccine composition with a mutant gB polypeptide and one or more T-cell epitopes. Additionally, a trivalent vaccine composition is envisioned, comprising three distinct mutant gB polypeptides with unique combinations of engineered disulfide mutations, providing broad protection against HCMV strains. Furthermore, an in vitro assembly system is proposed for high-yield production of prefusion-stabilized gB trimers, and a machine learning-based approach is developed for identifying novel HCMV gB mutations that enhance prefusion stability.

The new inventive concept introduces a paradigm shift in HCMV vaccine technology by incorporating multiple engineered disulfide mutations, optimized trimerization systems, and machine learning-based mutation prediction algorithms. These innovations provide a significant improvement over the original patent, enabling the development of more effective and broadly protective HCMV vaccines.

Alternative embodiments of the inventive concept could include the use of different vector systems, such as adenoviral or mRNA-based vectors, or the incorporation of additional immunogenic components, like Toll-like receptor agonists. Variations of the trivalent vaccine composition could include different combinations of mutant gB polypeptides or the addition of other HCMV antigens.

The next-generation HCMV vaccine technology has significant commercial potential in the vaccine market, particularly in the context of maternal and fetal health, as well as in immunocompromised populations. The inventive concept could be licensed to pharmaceutical companies or vaccine manufacturers, or developed in-house by Pfizer Inc. for commercialization.