期刊
SCIENCE ADVANCES
卷 8, 期 3, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abk2039
关键词
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资金
- National Institute of Allergy and Infectious Diseases
- Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [UM1AI100663]
- Center for HIV/AIDS Vaccine Development [UM1AI144462, P01 AI110657]
- Bill & Melinda Gates Foundation
- Collaboration for AIDS Vaccine Discovery (CAVD) [OPP1115782/INV-002916]
- NIH F31 Ruth L. Kirschstein Predoctoral Award [AI131873, S10 OD026799]
- Achievement Rewards for College Scientists Foundation
- amfAR Mathilde Krim Fellowships in Biomedical Research [110182-69-RKVA]
- NIH/NIAID [K99 AI123498]
- IAVI Neutralizing Antibody Center through the CAVD
- [P51 OD011132]
A hybrid approach combining structural and bioinformatic methods is presented for the identification and synthesis of monoclonal antibodies from serum-derived polyclonal antibodies, allowing for analysis of immune responses and iterative vaccine design.
One of the rate-limiting steps in analyzing immune responses to vaccines or infections is the isolation and characterization of monoclonal antibodies. Here, we present a hybrid structural and bioinformatic approach to directly assign the heavy and light chains, identify complementarity-determining regions, and discover sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen. When combined with next-generation sequencing of immune repertoires, we were able to specifically identify clonal family members, synthesize the monoclonal antibodies, and confirm that they interact with the antigen in a manner equivalent to the corresponding polyclonal antibodies. This structure-based approach for identification of monoclonal antibodies from polyclonal sera opens new avenues for analysis of immune responses and iterative vaccine design.
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