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A new method developed at The Scripps Research Institute uses cryo-electron microscopy to more quickly identify antibodies for vaccine development
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In this example, the algorithm sifted through approximately 100,000 to 1,000,000 possible antibody sequences from the database to determine the sequence (left) that best matched the antibody observed in the cryoEM image (transparent grey surface)
Scientists at Scripps Research have invented a method that may shorten a giant leap in modern vaccine development
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The researchers' work, published in the journal Science Advances on January 19, 2022, shows that they can rapidly characterize a vaccine or infection using high-resolution, cryo-electron microscopy (cryoo-EM).
Raised antibodies that bind to targets on the virus at the atomic level
The study's senior author, Dr.
Andrew Ward, Professor of Integrative Structural and Computational Biology at the Scripps Research Institute, said: "The COVID-19 pandemic has highlighted the need for robust and rapid vaccines and antiviral technologies
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We are optimistic that , our new approach will help meet this need by greatly simplifying antibody discovery
"Traditionally, identifying useful antibodies to viruses has required laborious sorting and testing of antibody-producing B cells to find the right antibodies -- a process that takes months," said a postdoctoral research associate and the study's first author.
Author Dr.
Aleksandar Antanasijevic said
.
"With this new method, we can go from collection of blood samples from infected or immunized patients to identification of all elicited antibodies of interest in about 10 days," said the study's co-first author, a staff member Scientist Charles Bowman added
.
The researchers' achievement is due in part to recent improvements in cryo-electron microscopy techniques
.
Cryo-electron microscopy is a technique that utilizes an electron beam to illuminate and image a target much lower than that of an ordinary light microscope
In the new study, the team took this research direction one step further
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They employed a "structure-sequence" computer algorithm that can link the antibody structure determined by cryo-electron microscopy to the DNA sequence that produced the structure
The researchers say they can confirm the accuracy of the results by replicating the unique "monoclonal" antibody using sequence data and verifying with cryo-EM that the antibody binds in the same way as the original imaged antibody
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Scientists are now refining their technology to optimize its speed and usability, and applying it to several areas: rapid assessment of human antibody responses to experimental HIV vaccines; development of antibody-blocking therapies for autoimmune diseases; and discovered antibodies capable of treating other protein targets on cells
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They anticipate that future improvements in cryo-EM techniques and structure-sequencing algorithms will allow faster identification of antibodies using only high-resolution structural images, without the need for DNA sequencing of B cells
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"This structure-to-sequence approach has great potential in immunology and other fields," Antanasijevic said.
"
We envision it could one day be used to study protein-protein interactions, for example, to discover the binding partners of specific proteins
.
"
From structure to sequence: Antibody discovery using cryoEM
