Researchers have outlined a new method for screening a person’s set of antibodies for rapid discovery of new drug molecules and vaccines for diseases like Ebola, HIV, flu and Epstein-Barr virus. The paper was published in Nature Biotechnology.
The research was done by scientists at the University of Kansas who wanted to get around the limitations of single-cell cloning for drug therapy development. While single-cell cloning has been effective for drug discovery in the past, it is expensive and limited to sampling a tiny fraction of possible human antibodies.
To do this, they created a screening platform that can screen millions of B cells for natively paired human antibody repertoires. The platform focuses on the variable VH and VL regions which are most important for antigen recognition. Using this platform, the team was able to identify HIV-1 broadly neutralizing antibodies and antibodies that neutralize against Ebola virus glycoprotein.
"Non-natural gene pairing has been used in the past because it's so much easier to do, but often the quality of antibodies discovered is not good enough for an effective drug, and the synthetic nature of those antibodies makes it difficult to understand the true human immune response," said co-lead author Brandon DeKosky, assistant professor of chemical & petroleum engineering and pharmaceutical chemistry at the University of Kansas. "By maintaining native antibody gene pairings throughout our process, we identified antibodies as they occurred naturally. Along the way, we found extremely potent antibodies and learned more about the human immune response to vaccination and natural infection."
This technology will be applied in future experiments for drug discovery against a broad range of disease targets.