Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody.

ABSTRACT: Broadly neutralizing antibodies (bnAbs) that neutralize diverse variants of a particular virus are of considerable therapeutic interest. Recent advances have enabled us to isolate and engineer these antibodies as therapeutics, but eliciting them through vaccination remains challenging, in part due to our limited understanding of how antibodies evolve breadth. Here, we analyze the landscape by which an anti-influenza receptor binding site (RBS) bnAb, CH65, evolved broad affinity to diverse H1 influenza strains. We do this by generating an antibody library of all possible evolutionary intermediates between the unmutated common ancestor (UCA) and the affinity-matured CH65 antibody and measure the affinity of each intermediate to three distinct H1 antigens. We find that affinity to each antige

SUBMITTER: Phillips AM 

PROVIDER: S-EPMC9995116 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature