Engineered chimeric fusion proteins

Enhancing stability and expression for improved vaccines and diagnostics in hMPV and RSV

The invention describes engineered chimeric F proteins combining sequences from human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) to enhance stability and expression. These proteins are useful in vaccines, diagnostics, and antibody screening.

Background

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are significant causes of respiratory tract infections, particularly in vulnerable populations such as infants, the elderly, and immunocompromised individuals. Despite the high disease burden, effective vaccines for both viruses remain elusive. Current approaches, including passive immunization, provide limited protection and are primarily used in high-risk infants.

The challenge in developing vaccines stems from the structural complexity and instability of the viral fusion (F) proteins, which undergo conformational changes that complicate the induction of a robust immune response. Stabilizing these proteins in their prefusion conformation is crucial for eliciting neutralizing antibodies, but achieving this stability without compromising protein expression and functionality has been a major hurdle. Existing methods have not yet succeeded in producing a vaccine that offers broad and long-lasting protection against these pervasive viruses.

Technology description

The engineered chimeric F proteins derived from human metapneumovirus and respiratory syncytial virus are designed to enhance conformational stability, thermostability, and expression levels. These proteins are composed of specific amino acid sequences from both hMPV and RSV, arranged to form an ectodomain. The sequences are selected for their high identity to known sequences, ensuring the retention of critical structural features. The proteins may include engineered disulfide bonds and specific amino acid substitutions to further stabilize the prefusion conformation.

These chimeric proteins are applicable in vaccine formulations, diagnostic assays, and antibody screening platforms. Additionally, methods for producing these proteins and their use in pharmaceutical compositions are included, potentially as part of a vaccine to prevent infections caused by hMPV or RSV.

The technology is differentiated by its ability to stabilize the prefusion conformation of the F proteins, which is crucial for effective vaccine development. The chimeric design combines elements from both hMPV and RSV, leveraging the structural similarities between these viruses to create a more stable and effective antigen.

This approach addresses the challenge of developing vaccines for viruses that have historically been difficult to target due to their structural instability. By enhancing the stability and expression levels of the F proteins, this technology offers a promising solution for creating vaccines that can elicit strong immune responses, potentially leading to more effective prevention of respiratory infections caused by these viruses.