Related Experiment Video
Updated: Sep 30, 2026

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Epistasis and pleiotropy constrain the evolution of cross-reactive breadth in a broadly neutralizing influenza
Katrine E Dailey1, Yiquan Wang2, Qi Wen Teo1,3
1Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois, United States of America.
Abstract:
The highly conserved influenza virus hemagglutinin (HA) stem domain is a major target for broadly neutralizing antibodies (bnAbs). However, despite being discovered more than a decade ago, the IGHV1-69-encoded CR9114 remains the only HA stem bnAb that cross-reacts with both influenza A and B viruses. To investigate the constraints on the breadth evolution of CR9114, this study performs four deep mutational scanning experiments to compare the binding affinity landscapes of the germline and somatic CR9114 against H1 HA, H3 HA, and influenza B virus HA. Many mutations that minimally affect or even improve the H1 HA binding are detrimental for binding to H3 HA and influenza B virus HA. We further reveal the prevalence of epistasis in IGHV1-69 HA stem bnAbs. Overall, our findings provide a mechanistic explanation for the scarcity of HA stem bnAbs with cross-reactivity against both influenza A and B viruses, and have important implications for developing broadly protective influenza vaccines.
Related Concept Videos
Cross-reactivity
Epistasis
Epistasis Analysis
Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Viral Recombination
Leaky Scanning

