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Technique Developed for High-Speed Antibody Screening

Human B-cell

Human B-cell (NIAID, Flickr)

18 January 2018. A process is being developed to quickly discover antibodies in a person’s immune system that can also lead to new vaccines and drugs against viruses. Researchers from University of Kansas in Lawrence, University of Texas in Austin, and the Vaccine Research Center at National Institutes of Health reported their findings in the 8 January issue of the journal Nature Biotechnology (paid subscription required).

The team of bio- and chemical engineering researchers is seeking better methods for identifying antibodies in human blood, to better understand immune system processes, as well as design more effective vaccines and treatments for diseases. Antibodies are proteins produced in the immune system to fight invading pathogens like bacteria or viruses, including current public health challenges like influenza and HIV.

Researchers from the labs of Brandon DeKosky at Kansas, Andrew Ellington and George Georgiou at Texas, and John Mascola at the National Institute of Allergy and Infectious Diseases in NIH focused on B-cells, white blood cells in the immune system that produce antibodies. Genes in B-cells encode the instructions for producing antibody proteins, containing amino acids known as heavy and light chains with the specific binding regions in the disease antigen, offering the targets for antibodies.

“The VH and VL portions — derived from the heavy and light chains, respectively,” says DeKosky in a University of Kansas statement, “are the sections of an antibody gene that provide specific viral targeting. So, the VH and VL portions are the most important region to focus on for antibody screening and discovery.” Previous attempts to screen for antibodies required cloning of single cells, a time-consuming and expensive process, yielding only a small part of the antibody inventory. This problem could be overcome by matching synthetic and natural genes, but the authors say the results are often lower in quality.

The new technique maintains the native gene pairings that naturally produce antibodies. The process uses amplicons, pieces of DNA or RNA amplified by genomic sequencing techniques such as polymerase chain reactions, building on previous advances in protein display and antibody discovery technologies. The team tested their process with blood samples, which screened millions of B-cells to reveal antibodies for neutralizing HIV-1, Ebola, and influenza viruses.

The authors say the technology offers a platform for wide-ranging basic and applied research discoveries, including new vaccines and therapies. “Promising sources to discover new antibodies include donated blood samples from HIV patients with powerful immune responses against the virus,” notes DeKosky, “and also individuals who have received vaccines so that we can understand how those vaccines are working. When a potently neutralizing antibody is discovered, it can lead to new vaccine strategies and new therapeutic drug candidates.”

University of Texas, where the initial research began, filed for a patent on the technology, with DeKosky, Ellington, and Georgiou listed among the inventors.

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