2026-10-11T22:37:31Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34017113 2026-09-28T17:40:04Z category_4 category_8 category_24 category_734 category_132 category_134 portal_5 item_type_3 month_year_09_2026

<p>Forward primers for mutant library construction.</p> Katrine E. Dailey (25132772) Yiquan Wang (109363) Qi Wen Teo (17439774) Chaoyang Wang (1469923) Huibin Lv (820375) Ruipeng Lei (4007048) Meixuan Tong (25132775) Lucia A. Rodriguez (25132778) Letianchu Wang (25132781) Nicholas C. Wu (8592198) Biochemistry Microbiology Evolutionary Biology Biological Sciences not elsewhere classified Infectious Diseases Virology broadly neutralizing antibodies binding affinity landscapes encoded cr9114 remains ha stem bnab ha stem bnabs h1 ha binding h1 ha stem domain bnabs ). h3 ha xlink "> somatic cr9114 reactive breadth pleiotropy constrain minimally affect mechanistic explanation many mutations major target important implications findings provide even improve decade ago b viruses <div><p>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.</p></div> 2026-09-28T18:03:20Z Dataset Dataset 10.1371/journal.pbio.3004021.s013 https://figshare.com/articles/dataset/_p_Forward_primers_for_mutant_library_construction_p_/34017113 CC BY 4.0