Main Conference Day 2Thursday, 28 May 2026 - European Time GMT+1

Bispecific antibodies (bsAbs) can enable therapeutic mechanisms, such as dual antigen targeting or receptor agonism, that are impossible using monoclonal antibodies. BsAbs with IgG-like format (bsIgG) are comprised of two unique heavy chains, each having a cognate light chain. Co-expression of these four unique polypeptides often leads to several mispaired species that are difficult to separate from the target bsIgG due to their similar biophysical properties. Here we describe a set of mutations called ProAla that exploit a the unfolded protein response pathway of cells. ProAla heavy chains are engineered with higher folding energy barriers such that only the cognate light and heavy chains can induce folding, chaperone release and secretion. The structures of the ProAla Fab and Fc regions are identical in structure to normal antibodies, enabling maintenance of half-life and function. Mispaired polypeptides fail to secrete from the cell due to enhanced interaction with the endoplasmic reticulum chaperone BiP, resulting in increased purity of secreted bsIgGs.

TCR specificity to peptide-HLA antigens is central to immunology, impacting responses in infection, autoimmunity and cancer. Achieving precise recognition while avoiding off-target reactivity is critical for effective immunity and safe therapeutic interventions. Comprehensive, proteome-wide specificity profiling of TCRs is challenging with current methods, which notably lack integrated machine learning for large-scale analysis. Here, we report a synthetic immune cell system coupled with machine learning to enable TCR functional and specificity mapping of peptide-HLA antigens at proteome-scale.

Influenza A viruses pose a persistent public health challenge due to antigenic diversity, rapid evolution, and zoonotic reservoirs with pandemic potential, as highlighted by recent H5N1 spillover from cattle to humans. Immune history shaped by repeated exposure complicates both prevention and therapy. We show how isolating and functionally characterizing human hemagglutinin-targeting antibodies reveals cross-reactive immunity, identifies conserved vulnerabilities, and informs strategies for antibody-based therapeutics and vaccine design.

Monkeypox is a dangerous virus, and some of its key targets for immunity are still unknown. We discovered antibodies that recognize a viral protein called A28 and showed they can strongly neutralize Monkeypox and related viruses. Vaccinating mice with A28 triggered powerful immune responses and fully protected them from infection. These results suggest A28 could improve future Monkeypox vaccines.

Serological antibodies represent an immunologically distinct compartment from B-cell repertoires that is often overlooked by genetic methods. A novel proteomics platform enables standalone protein-level discovery from complex human serum, sequencing unique antibodies absent in B-cell data. In a COVID-19 benchmark with zero prior B-cell neutralizers, we identified 18 distinct clones, yielding 8 neutralizers (3 highly potent, <0.2 µg/mL IC50), facilitating a pathway to real-world therapeutic discovery across diseases.

Neonatal Fc receptor is a popular target for treatment of autoimmune disorders due to its role in maintaining IgG levels. Fc-ABDEG and albumin-binding VHH were combined to develop next-generation FcRn blockers with improved IgG clearance. Step-wise engineering was applied to optimize position and number of VHHs, their affinity to albumin, and the linker connecting it to Fc-ABDEG. Novel FcRn-based cellular assays and effects in human FcRn transgenic mice are included.