Librator: a platform for the optimized analysis, design, and expression of mutable influenza viral antigens.

TitleLibrator: a platform for the optimized analysis, design, and expression of mutable influenza viral antigens.
Publication TypeJournal Article
Year of Publication2022
AuthorsLi L, Changrob S, Fu Y, Stovicek O, Guthmiller JJ, McGrath JJC, Dugan HL, Stamper CT, Zheng N-Y, Huang M, Wilson PC
JournalBrief Bioinform
Date Published2022 03 10
KeywordsAntibodies, Viral, Antigens, Viral, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Influenza Vaccines, Influenza, Human, Neuraminidase, Orthomyxoviridae

Artificial mutagenesis and protein engineering have laid the foundation for antigenic characterization and universal vaccine design for influenza viruses. However, many methods used in this process require manual sequence editing and protein expression, limiting their efficiency and utility in high-throughput applications. More streamlined in silico tools allowing researchers to properly analyze and visualize influenza viral protein sequences with accurate nomenclature are necessary to improve antigen design and productivity. To address this need, we developed Librator, a system for analyzing and designing custom protein sequences of influenza virus hemagglutinin (HA) and neuraminidase (NA) glycoproteins. Within Librator's graphical interface, users can easily interrogate viral sequences and phylogenies, visualize antigen structures and conservation, mutate target residues and design custom antigens. Librator also provides optimized fragment design for Gibson Assembly of HA and NA expression constructs based on peptide conservation of all historical HA and NA sequences, ensuring fragments are reusable and compatible across related subtypes, thereby promoting reagent savings. Finally, the program facilitates single-cell immune profiling, epitope mapping of monoclonal antibodies and mosaic protein design. Using Librator-based antigen construction, we demonstrate that antigenicity can be readily transferred between HA molecules of H3, but not H1, lineage viruses. Altogether, Librator is a valuable tool for analyzing influenza virus HA and NA proteins and provides an efficient resource for optimizing recombinant influenza antigen synthesis.

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Alternate JournalBrief Bioinform
PubMed ID35183062
PubMed Central IDPMC8921739
Grant ListU19 AI057266 / AI / NIAID NIH HHS / United States
HHSN272201400005C / AI / NIAID NIH HHS / United States
U19 AI082724 / AI / NIAID NIH HHS / United States
U19 AI109946 / AI / NIAID NIH HHS / United States

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