biostudies-literatureSevy AMNIAID NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesVanderbilt UniversityNIH HHS1597-1602https://www.ebi.ac.uk/biostudies/studies/S-EPMC6358683biostudies-literatureUnknown116(5)Influenza is a yearly threat to global public health. Rapid changes in influenza surface proteins resulting from antigenic drift and shift events make it difficult to readily identify antibodies with broadly neutralizing activity against different influenza subtypes with high frequency, specifically antibodies targeting the receptor binding domain (RBD) on influenza HA protein. We developed an optimized computational design method that is able to optimize an antibody for recognition of large panels of antigens. To demonstrate the utility of this multistate design method, we used it to redesign an antiinfluenza antibody against a large panel of more than 500 seasonal HA antigens of the H1 subtype. As a proof of concept, we tested this method on a variety of known antiinfluenza antibodies anProceedings of the National Academy of Sciences of the United States of AmericaMultistate design of influenza antibodies improves affinity and breadth against seasonal viruses.PMC6358683Trans-Institutional ProgramU19 AI117905S10 OD023680Sevy AMBurger SCrowe JEWu NCParrish EHWilson IANagel MBMYousif DSchey KLMeiler JGilchuk IMfalseMultistate design of influenza antibodies improves affinity and breadth against seasonal viruses.Influenza is a yearly threat to global public health. Rapid changes in influenza surface proteins resulting from antigenic drift and shift events make it difficult to readily identify antibodies with broadly neutralizing activity against different influenza subtypes with high frequency, specifically antibodies targeting the receptor binding domain (RBD) on influenza HA protein. We developed an optimized computational design method that is able to optimize an antibody for recognition of large panels of antigens. To demonstrate the utility of this multistate design method, we used it to redesign an antiinfluenza antibody against a large panel of more than 500 seasonal HA antigens of the H1 subtype. As a proof of concept, we tested this method on a variety of known antiinfluenza antibodies an2019-01-01T00:00:00Z2019 Jan2026-04-15T11:08:37.197Z2019-09-14T07:01:20ZS-EPMC63586833064296110.1073/pnas.1806004116