Convergent Sequence Features of Antiviral B Cells

Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, building diverse antigen-specific antibody repertoires. In recent years, these repertoires have become an important source for novel antibody-based antiviral therapeutics, yet there is still limited understanding of the determinants of antibody-antigen specificity. Here, we generated a large dataset mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against twenty viral antigens representing diverse pathogens of biomedical significance. Analysis revealed antigen-specific patterns in variable gene usage, gene pairing, and somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals. These results help define the characteristics of human antibody repertoires simultaneously against an unprecedented number and diversity of viral targets. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses. ### Competing Interest Statement A.A.A. and I.S.G. are listed as inventors on patents filed describing the antibodies discovered here. I.S.G. is listed as an inventor on patent applications for the LIBRA-seq technology. I.S.G. is a co-founder of AbSeek Bio. I.S.G. has served as a consultant for Sanofi. The Georgiev laboratory at VUMC has received unrelated funding from Merck and Takeda Pharmaceuticals.