Prevention of Alzheimer’s disease presents one of the most confounding challenges in modern medicine. The disease is thought to be caused by a combination of factors, the two main mechanisms being aberrantly formed beta-amyloid proteins aggregating into harmful plaques and tau proteins becoming hyperphosphorylated, leading to oxidative stress and neuronal damage.
Past therapies focused on clearing beta-amyloid plaques and were met with limited success. Now, a team at the Gates Biomanufacturing Facility (GBF) in collaboration with California-based Institute for Molecular Medicine (IMM) is taking an innovative approach: a dual-target vaccine. The GBF’s Biologics group developed two molecules, one targeting amyloid beta plaques and the other tau hyperphosphorylation, from tech transfer to process development to a large-scale current Good Manufacturing Practice (cGMP) manufacturing process for phase 1 human clinical trials. The two molecules are planned to go into clinical trials independently as well as combined to make a single drug product as a dual vaccine.
The GBF has been working for the past several years with the IMM to develop the vaccine. The two-pronged approach was developed after several prior clinical efforts stalled in later-stage clinical trials. Preclinical trials for the two molecules have been successfully completed, demonstrating efficacy, safety, and promising immunogenicity, the ability of a substance to prompt the body to make an immune response. The IMM is now working towards starting clinical trials in humans.
Developing a biological vaccine presents unique hurdles, including ensuring molecular stability, optimizing immunogenicity and ensuring quality control and safety measures. The development and manufacturing team, led by Gana Batt, PhD, with Supervisor of Biologics Operations Aashrit Donthi, and Process Engineer Caitlynn Pine, faced significant challenges in developing the vaccine’s soluble, oligomeric (composed of more than one molecule) protein formulations. Since the two targeted molecules, AV-1959R (targeting beta-amyloid plaque formation) and AV-1980R (targeting tau hyperphosphorylation), preferred different conditions for stability, achieving the right formulations required extensive fine-tuning. Rigorous quality control standards were maintained throughout development and manufacturing to ensure compliance with FDA regulations.
“Quality control and process development go hand in hand for us,” noted Donthi. “Development and scale up is performed with the safety assay limits in mind. We execute engineering runs at scale to make sure standards are met before clinical manufacture.”
As the GBF-IMM team works to secure regulatory approval, the hope is that this innovative vaccine will not only slow disease progression but also offer preventative protection against Alzheimer’s disease.
This collaborative effort highlights the cGMP expertise available at GBF, a pillar of the Gates Institute at the Anschutz Medical Campus and one of the few organizations of its kind in the nation for both cell therapy and biologics manufacturing.
With the potential to revolutionize the landscape of neurodegenerative disease treatment and prevention, this novel, dual-target Alzheimer’s vaccine represents a bold step forward in scientific innovation.
“We stand on the brink of a breakthrough,” Batt said. “One that could redefine Alzheimer’s treatment for generations to come.”
Photo at top: Aashrit Donthi and Caitlynn Pine presented their research in manufacturing an Alzheimer’s vaccine at the Colorado Protein Stability Conference in Breckenridge, Colorado.