skip to main content

Title: De novo sequencing and resurrection of a human astrovirus-neutralizing antibody

Monoclonal antibody (mAb) therapeutics targeting cancer, autoimmune diseases, inflammatory diseases, and infectious diseases are growing exponentially. Although numerous panels of mAbs targeting infectious disease agents have been developed, their progression into clinically useful mAbs is often hindered by the lack of sequence information and/or loss of hybridoma cells that produce them. Here we combine the power of crystallography and mass spectrometry to determine the amino acid sequence and glycosylation modification of the Fab fragment of a potent human astrovirus-neutralizing mAb. We used this information to engineer a recombinant antibody single-chain variable fragment that has the same specificity as the parent monoclonal antibody to bind to the astrovirus capsid protein. Furthermore, this antibody can now potentially be developed as a therapeutic and diagnostic agent.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [4] ;  [1]
  1. Univ. of California, Santa Cruz, CA (United States)
  2. New York Univ. School of Medicine, New York, NY (United States)
  3. Protein Metrics, San Carlos, CA (United States)
  4. Instituto de Salud Carlos III, Madrid (Spain)
Publication Date:
OSTI Identifier:
1244771
Grant/Contract Number:
AC02-05CH11231
Type:
Published Article
Journal Name:
ACS Infectious Diseases
Additional Journal Information:
Journal Volume: 2; Journal Issue: 5; Journal ID: ISSN 2373-8227
Publisher:
American Chemical Society (ACS)
Research Org:
Univ. of California, Santa Cruz, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; antibody; astrovirus; mass spectrometry; protein engineering; protein sequencing; X-ray crystallography