An antibody library created from healthy donors before the COVID-19 outbreak has yielded antibodies with therapeutic and diagnostic potential. They are specific to the SARS-CoV-2 virus and could be used in highly sensitive diagnostic assays. Some of the antibodies also prevented the virus from entering human cells, potentially useful as treatment to facilitate faster recovery from COVID-19.
“In our experiments we used a highly diverse, unexposed-antibody library, as such libraries have been shown to yield antibodies against any antigen,” said Nileena Velappan, first author on a paper in the journal Bioengineered. “We optimized the selection-and-screening process to identify antibodies with specific binding properties so they can distinguish between SARS-CoV-1 and SARS-CoV-2 and antibodies that recognize both viruses. This strategy allowed us to get a very diverse set.”
As an emerging disease, COVID-19 required the use of novel detection reagents for the virus, as well as new therapeutic molecules to treat seriously ill persons. Antibodies, the specialized proteins the immune system uses to neutralize pathogens, are well established as diagnostic reagents (for example, in at-home pregnancy tests) and serve as the first line of defense in our immune system against viruses.
The antibody discovery method developed by Velappan, Antonietta Lillo and their colleagues uniquely generated a rich repertoire of antibodies recognizing an unprecedented number of separate regions in the SARS-CoV-2 virus, noted corresponding author Lillo. Antibodies with these characteristics are necessary for both the specific recognition of a pathogen and for developing therapeutic antibody cocktails, she said. Antibody cocktails, more than single antibodies, are likely to retain their function despite the pathogen’s natural tendency to mutate.
“Follow-up work (manuscript is in preparation) shows that antibody F07, one of the best antibodies found in our study, recognizes not only the original strain of SARS-CoV-2 but also Delta and Omicron,” said Lillo. “This confirms that we have indeed found a rich repertoire of antibodies, among which F07 is uniquely cross-reactive. F07 might be one of those elusive antibodies that is active against any possible SARS-CoV-2 strains.”
Lillo noted that the results indicate that readily available nonimmune antibody libraries obtained from healthy donors can be used to select high-quality monoclonal antibodies, bypassing the need for the blood of infected patients.
“They offer a widely accessible and low-cost alternative to more sophisticated and expensive antibody selection approaches,” she said.
Paper: Healthy humans can be a source of antibodies countering COVID-19, Bioengineered, DOI: https://doi.org/10.1080/21655979.2022.2076390. Los Alamos authors: Nileena Velappan, Hau Nguyen, Sofiya Micheva-Viteva, Austin Watts, Bin Hu, Geoffrey Waldo, Antonietta Lillo.
Funding: Research was supported by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on response to COVID-19, with funding provided by the Coronavirus CARES Act. Additional funding was provided by the Los Alamos National Laboratory Directed Research & Development fund.