Influenza viruses continue to cause substantial morbidity and mortality worldwide. Fast gene mutation on
surface proteins of influenza virus result in increasing resistance to current
vaccines and available
antiviral drugs.
Broadly neutralizing antibodies (
bnAbs) represent targets for prophylactic and therapeutic treatments of
influenza. We performed a systematic bioinformatics study of cross-reactivity of
neutralizing antibodies (nAbs) against influenza virus
surface glycoprotein hemagglutinin (HA). This study utilized the available crystal structures of HA complexed with the
antibodies for the analysis of
tens of thousands of HA sequences. The detailed description of
B-cell epitopes, measurement of
epitope area similarity among different strains, and estimation of
antibody neutralizing coverage provide insights into cross-reactivity status of existing nAbs against influenza virus. We have developed a method to assess the likely cross-reactivity potential of
bnAbs for
influenza strains, either newly emerged or existing. Our method catalogs
influenza strains by a new concept named discontinuous
peptide, and then provide assessment of cross-reactivity. Potentially cross-reactive strains are those that share 100% identity with experimentally verified neutralized strains. By cataloging
influenza strains and their
B-cell epitopes for known
bnAbs, our method provides guidance for selection of representative strains for further experimental design. The knowledge of sequences, their
B-cell epitopes, and differences between historical
influenza strains, we enhance our preparedness and the ability to respond to the emerging pandemic threats.