July 2026 Literature Digest: Antibody and Protein Research Advances Featuring abinScience Products

Mpox virus (MPXV) has re-emerged in outbreaks worldwide in recent years, and existing vaccines (ACAM2000, JYNNEOS, LC16m8) and antiviral drugs (tecovirimat) offer only limited protection, underscoring the need for novel antibody therapies. The research team immunized BALB/c mice with A35R-Fc mRNA-LNP and, using the Beacon high-throughput single-cell sorting platform, rapidly isolated five neutralizing antibodies from splenic plasma cells targeting A35R, a surface protein of the MPXV extracellular enveloped virus (EEV). Among them, 17H1 performed best: its affinity for A35R reached 0.09 nM, with a neutralizing IC50 of 259.3 ng/mL. In a lethal-dose MPXV challenge mouse model, 17H1 achieved 100% survival protection whether given prophylactically (24 hours before challenge) or therapeutically (24 hours after challenge), and significantly reduced lung viral load and pathological damage. Cryo-EM analysis revealed that 17H1 binds a previously unreported conformational epitope at the distal end of the A35R dimer at a shallow angle of roughly 20°, with an R99–E120 salt-bridge network as the key binding site — a binding mode distinct from previously reported A35R/A33 antibodies. The findings indicate that 17H1 is a highly promising candidate therapeutic antibody against mpox, providing a new structural foundation for the development of EEV-targeted antibody drugs.

Frontotemporal dementia (FTD) is one of the most common causes of early-onset dementia, with approximately 5–10% of cases caused by loss-of-function mutations in the GRN gene, leading to markedly reduced levels of progranulin (PGRN) in patients. Blocking sortilin-mediated PGRN clearance to raise extracellular PGRN levels has therefore emerged as a promising therapeutic strategy. Existing antibody (latozinemab) and small-molecule (VES001) drugs have validated the feasibility of this target, but full-length IgG antibodies carry limitations such as molecular complexity and the risk of unintended Fc-mediated effects. This study, built on the non-immunoglobulin affibody scaffold, fused two moderate-affinity anti-sortilin affibodies (ZSort:A3 and ZSort:G11) using different orientations, linker lengths, and helix-truncation strategies to generate 10 heterodimeric constructs. Following SPR-based affinity screening and optimization, the team obtained lead molecules with picomolar-range affinity; notably, the 18.6 kDa D4 construct alone achieved an EC50 as low as 0.32 nM in PGRN clearance assays, substantially outperforming the monomeric forms, and was accompanied by reduced cell-surface and total sortilin levels, confirming its receptor-blocking effect. The findings suggest that compact, modular biparatopic affibody molecules could serve as an alternative to conventional antibody therapies, offering a new tool for exploring the sortilin pathway in neurodegenerative disease, inflammation, and oncology.

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) encodes numerous lineage-enriched transcriptional regulators that are absent or poorly conserved in non-pathogenic K-12 strains, yet their role in regulating biofilm-associated virulence had not previously been systematically characterized. Through comparative genomic analysis, this study screened 1,442 genes unique to the O157:H7 Sakai strain and identified 8 previously unreported biofilm-related transcriptional regulators (spanning multiple families including LysR, GntR, LuxR, AraC/XylS, Cro/CI, and Ogr/Delta). Among these, ECs_2620 and ECs_4457 were confirmed as direct DNA-binding transcriptional regulators through in vitro and in vivo DNA-binding assays, and their specific DNA-binding motifs were identified. Functional experiments showed that overexpressing these 8 regulators enhanced biofilm formation, while gene knockout significantly impaired biofilm development and reduced bacterial virulence in THP-1 cells and mouse infection models. Transcriptomic analysis revealed that these regulators act mainly by controlling genes related to chemotaxis and flagellar assembly, forming a regulatory framework distinct from the classical c-di-GMP-centered paradigm seen in non-pathogenic E. coli. Evolutionary analysis further showed that these regulators are highly conserved across pathogenic E. coli lineages such as EHEC, EPEC, and ETEC, but are absent or truncated in non-pathogenic K-12 strains. The study offers new insight into the macromolecular regulation of biofilm formation and virulence in pathogenic E. coli, and points to potential targets for anti-virulence intervention strategies.