Biology subjects

Becker, J. E.

Publications and source records attributed to Becker, J. E..

4 recordsLinked to original sources

bioRxiv2026

A Panel of Human Monoclonal Antibodies for Tracking the Antigenic Evolution of Influenza H5N1 Clade 2.3.4.4b

The ongoing panzootic of clade 2.3.4.4b H5N1 influenza has resulted in widespread infection of birds, mammals, and livestock, underscoring the need for tools to interpret its real-time evolution. Here, we describe the isolation and characterization of a panel of 19 human monoclonal antibodies that potently neutralize current isolates. Competition immunoassays and cryo-electron microscopy analyses revealed their collective near-complete epitope coverage of the H5-hemagglutinin surface. Neutralization profiling across multiple historical and contemporary H5 viruses defined their epitope-specific patterns of virus neutralization. One cluster of antibodies potently neutralized only clade 2.3.4.4b viruses, while many others exhibited broadly neutralizing activity against diverse H5N1 clades. Application of this structurally calibrated antibody panel to recent North American human isolates revealed genotype-specific antigenic divergence between lineages that have spread among cattle (B3.13) and poultry (D1.1). Together, the findings of this study establish a structurally grounded antibody reference panel spanning major vulnerable sites of H5 hemagglutinin and provide a toolbox for interpreting emergent mutations, monitoring ongoing antigenic drift, and anticipating the evolutionary trajectory of circulating H5N1 influenza viruses.

microbiology↗

bioRxiv2025

Vaccine Elicitation of HIV-1 Neutralizing Antibodies Against Both V2 Apex and Fusion Peptide in Rhesus Macaques

Broadly neutralizing antibodies targeting multiple sites of HIV-1 Env vulnerability can be induced by infection, but simultaneous elicitation of neutralizing antibodies (NAbs) against multiple epitopes has not yet been achieved by vaccination. In this study, we designed a dual-epitope vaccine targeting both fusion peptide (FP) and V2 apex and evaluated its capacity to induce NAbs against both epitopes in rhesus macaques. This vaccine combined an FP conjugate with a cocktail of engineered Env trimers with enhanced V2 apex recognition and increased antigen retention in lymph nodes. Immunization of macaques with the dual-epitope vaccine elicited >1000-fold higher autologous tier 2-neutralization titers than the wildtype Env trimer and enhanced heterologous NAb breadth. Both FP and V2-apex monoclonal antibodies (mAb) were isolated from immunized macaques and showed heterologous neutralization with genetic and structural signatures that were similar to well-characterized FP and V2 apex bNAbs, although the V2 apex mAbs showed incomplete maturation. These results demonstrate proof-of-concept for simultaneous vaccine elicitation of NAbs against multiple sites of Env vulnerability, which will likely be critical for an effective HIV-1 vaccine. HIGHLIGHTSO_LIDesigned a dual-epitope vaccine targeting both fusion peptide (FP) and V2 apex C_LIO_LIV2-SET Env trimer conferred higher binding of V2 apex bNAbs, longer retention in draining lymph nodes, and >1000-fold higher induction of autologous neutralization titers compared with wildtype Env trimer C_LIO_LIDual-epitope vaccine enhanced serum tier 2 neutralization breadth C_LIO_LIDual-epitope vaccine elicited FP- and V2 apex-specific neutralizing mAbs with genetic signatures similar to well-characterized FP and V2 apex bNAbs C_LI

immunology↗

bioRxiv2024

Structure of a zoonotic H5N1 hemagglutinin reveals a receptor-binding site occupied by an auto-glycan

Highly pathogenic avian influenza has spilled into many mammals, most notably U.S. dairy cows with several dozen human breakthrough infections. Zoonotic crossovers, with hemagglutinins mutated to enhance viral ability to use human 2-6-linked sialic acid receptors versus avian 2-3-linked ones, highlight the pandemic risk. To gain insight into these crossovers, we determined the cryo-EM structure of hemagglutinin from the zoonotic H5N1 A/Texas/37/2024 strain (clade 2.3.4.4b) in complex with a previously reported neutralizing antibody. Surprisingly, we found that the receptor-binding site of this H5N1 hemagglutinin was already occupied by an 2-3-linked sialic acid and that this glycan emanated from asparagine N169 of a neighboring protomer on hemagglutinin itself. This structure thus highlights recognition by influenza hemagglutinin of an "auto"-2-3-linked sialic acid from N169, an N-linked glycan conserved in 95% of H5 strains, and adds "auto-glycan recognition" to the complexities surrounding H5N1 zoonosis. HighlightsO_LIWe report the structure of hemagglutinin from the zoonotic H5N1 strain A/Texas/37/2024 from clade 2.3.4.4b responsible for the current H5N1 outbreak C_LIO_LIStructural analysis revealed that each receptor-binding site of H5N1 A/Texas/37/2024 HA is bound to an "auto" sialic acid originating from glycan N169 on an adjacent protomer C_LIO_LIThis structure provides new aspects of receptor binding for a highly pathogenic strain of avian influenza, and raises questions about the impact of auto-binding sialic acid, especially with respect to zoonosis C_LI

immunology↗

bioRxiv2024

Cis inhibition of co-expressed DIPs and Dprs shapes neural development

In Drosophila, two interacting adhesion protein families, Dprs and DIPs, coordinate the assembly of neural networks. While intercellular DIP/Dpr interactions have been well characterized, DIPs and Dprs are often co-expressed within the same cells, raising the question as to whether they also interact in cis. We show, in cultured cells and in vivo, that DIP- and DIP-{delta} can interact in cis with their ligands, Dpr6/10 and Dpr12, respectively. When co-expressed in cis with their cognate partners, these Dprs regulate the extent of trans binding, presumably through competitive cis interactions. We demonstrate the neurodevelopmental effects of cis inhibition in fly motor neurons and in the mushroom body. We further show that a long disordered region of DIP- at the C-terminus is required for cis but not trans interactions, likely because it alleviates geometric constraints on cis binding. Thus, the balance between cis and trans interactions plays a role in controlling neural development.

biochemistry↗