The COVID-19 pandemic has generated an urgent need for a vaccine. Investigators worldwide are scrambling to help, including global researchers using software developed in the laboratory of Wayne State University Associate Professor of Pediatrics Alan Dombkowski, Ph.D.
The studies could lead to rapid development of a SARS-CoV-2 vaccine.
“Four academic publications recently submitted to preprint servers by international research groups report their work toward developing a COVID-19 vaccine using a technique called immunoinformatics. It is a computer-driven approach, and a key step uses our software, Disulfide by Design,” Dr. Dombkowski said.
Dr. Dombkowski is an internationally-recognized expert on disulfide engineering, a key step in a newer, streamlined method of potential vaccine development called immunoinformatics. Immunoinformatics employs a computer-driven approach to identifying fragments of the target pathogen that would provide a suitable vaccine, avoiding potential safety concerns from the more traditional approach of using whole pathogens.
Computational techniques can predict locations in a protein or peptide where disulfide bonds can be introduced. Several peptide fragments from different proteins of the virus can be linked together and simultaneously provide immunity for different strains of a virus or to ensure coverage of different stages of the viral life cycle, known as multi-epitope peptide vaccine, or MEPV, development.
“The three-dimensional structure of a vaccine is very important to its recognition by an antibody, akin to a lock and key,” Dr. Dombkowski explained. “A weakness of using protein fragments is that they are often unstable and easily unfold. However, the stability of peptide vaccines can be increased by introducing artificial bonds that stitch the peptide strands together.”
The classical approach to developing vaccines relies on inactivated or attenuated whole pathogens to which the body develops antibodies, protecting an individual from future exposure. The approach includes a lengthy development cycle, production challenges, the potential of incomplete inactivation and allergic responses.
The production of peptide-based vaccines is much simpler, faster and cost-effective compared to the classical whole pathogen approach.
The web-based tool developed by Dr. Dombkowski and Department of Oncology Research Assistant Douglas Craig called “Disulfide by Design 2” (DbD2) was used by scientists in Bangladesh, Belgium, Malaysia and Pakistan to accomplish the critical step of vaccine stabilization in their immunoinformatics approach to identifying potential SARS-CoV-2 vaccines.