The fight against respiratory syncytial virus (RSV) has taken a significant step forward with the development and validation of a groundbreaking 3D Vaxlock platform technology by Calder Biosciences. This innovative approach, focusing on the RSV fusion (F) protein, has demonstrated an 11-fold increase in immune response effectiveness compared to traditional methods, according to a study published in Nature Communications.
RSV virion structure. Image Credit: NIAID
The Power of Prefusion F Protein Stabilization
Recent research highlights the crucial role of fusion proteins in triggering antibody responses that combat viral infections and serve as a predictor of vaccine efficacy. Dityrosine (DT) bonds, naturally occurring structures that enhance protein rigidity, are at the heart of this new technology. By strategically crosslinking DT bonds, researchers can stabilize the RSV F protein in its prefusion conformation. This stabilization is key to optimizing vaccine immunogens and maximizing neutralizing antibody responses, leading to enhanced protection against RSV.
Addressing Unmet Needs in RSV Prevention
While existing RSV vaccines have shown some success, particularly in older adults, a critical need remains for more effective prevention strategies, especially for individuals over 75 and those with weakened immune systems (immunosenescence). As Dr. Florian Schödel, a member of Calder’s Scientific Advisory Board, emphasizes, “There remains an urgent need for vaccines that provide older adults [aged 75 plus] and the frail good protection. Protecting newborn children for a longer period through maternal vaccination also remains an important goal.”
How 3D Vaxlock Technology Works
The 3D Vaxlock technology employs a precise method of creating DT crosslinks within the prefusion F (preF) protein. This process, involving structure-based design and site-directed mutagenesis, targets specific epitopes crucial for inducing a robust immune response. These engineered DT crosslinks “lock” the preF protein in its optimal conformation, ensuring a highly targeted and effective antibody response.
Respiratory syncytial virus (RSV) causing respiratory infections. Image Credit: Artur | stocck.adobe.com
Calder’s 3D Vaxlock technology utilizes zero-length carbon-carbon bonds between tyrosine residues in the vaccine immunogens. This innovative approach combines structure-based design and a novel bioprocess to create site-specific bonds, strategically placed to preserve the 3D structure of the preF protein in regions critical for eliciting a strong immune response.
Promising Results and Future Implications
The study results demonstrate an impressive 11-fold increase in neutralizing antibody responses, suggesting a significant improvement in preventing RSV infection. This enhanced immune response translates to better protection and potentially a longer shelf-life for the RSV vaccine. Chris Marshall, co-founder and CEO of Calder Biosciences, highlights the importance of this technology: “A new stabilization technology as clean and precise as this one is exactly what’s needed to unlock the full potential of protein vaccines. Unlike disulfide bonds, [DT] bonds are irreversible, and their formation is catalyzed after the protein is fully folded in its native state.”
Conclusion: A New Era in RSV Vaccination?
The development of 3D Vaxlock technology marks a significant advancement in RSV vaccine development. By precisely engineering DT crosslinks within the preF protein, this technology enhances immune response and offers a promising path toward more effective RSV prevention for vulnerable populations. While further research and clinical trials are necessary, this breakthrough offers hope for a future with improved protection against this common and potentially serious respiratory virus. For personalized treatment plans and vaccination advice, consult with a healthcare professional.
References
Calder Biosciences Inc. Publishes Next-Generation Vaccine Technology in Nature Communications. PR Newswire. News release. March 14, 2024. Accessed March 28, 2024. https://www.prnewswire.com/news-releases/calder-biosciences-inc-publishes-next-generation-vaccine-technology-in-nature-communications-302089350.html.
Engineered dityrosine-bonding of the RSV prefusion F protein imparts stability and potency advantages. Nature Communications. News release. March 14, 2024. Accessed March 28, 2024. https://www.nature.com/articles/s41467-024-46295-8.
