At Alchemab, we are harnessing the power of the immune system to counter complex diseases. By mining the antibody repertoires of individuals who demonstrate exceptional resilience to disease we are able to pinpoint antibodies which are linked to improved outcomes. Selected antibodies are characterised by function and target specificity before entering preclinical disease models. We will show examples to illustrate the platform’s applicability across disease areas, including Infection, Oncology and Neurodegeneration.

This presentation will introduce Berkeley Lights’ Opto™ Plasma B Discovery 4.0 workflow that enables recovery of 1000s of hits by screening up to 100,000 plasma cells, down-selection of lead candidates by functional screening, and sequencing and re-expression of >1000 functionally-characterized antibodies all in 1 week. By maximizing the diversity of antibodies through direct functional profiling of plasma cells, the OPBD 4.0 workflow allows users to tackle even the most challenging targets.

Memo Therapeutics embarked on the race to develop an antibody-based medicine for COVID-19 in April 2020. Using our microfluidic single-cell-based RT-PCR and recombinant mammalian expression technology Dropzylla, we generated recombinant antibody repertoire biobanks from clinically selected convalescent COVID-19 donors. Screening of the repertoire libraries yielded a large portfolio of SARS-CoV-2-neutralizing antibodies against a multitude of possible variants of SARS-CoV-2 in less than one month. Our selected candidate, CoVAb36 showed picomolar neutralization of wt SARS-CoV-2 and good developability and yield in a fast track GMP production process.

Here, we describe the longitudinal kinetics of the serological memory in COVID-19 recovered patients over the period of 14 months. The decay rate is associated with the robustness of the response and the decay was significantly slower compared to naïve vaccinees, suggesting that the serological memory following natural infection is more robust compared to vaccination. These data highlight the possible superiority of hybrid immunity.

• ?NEW TALK - This Presentation Will be Given for the First Time

As the pandemic continues, more transmissible SARS-CoV-2 variants that evade COVID-19 treatments have emerged. As part of its ongoing pandemic response, AbCellera discovered a highly potent monoclonal antibody, bebtelovimab (LY-CoV1404) from a convalescent COVID-19 patient sample that could present a long-term solution to the ongoing pandemic. Bebtelovimab targets a rarely-mutated epitope on the SARS-CoV-2 spike protein and potently neutralizes variants of concern, including the Delta variant.

Although antibody success in the clinic can often be achieved with blocking antibodies, it is more difficult to create antibodies that intracellularly signal in positive (agonistic) or negative (antagonistic) ways especially as it relates to the TNF superfamily of receptors. We focus on the creation of extracellular hexagonal networks with strategically binding antibodies to the cell surface with an emphasis on the TNFR2 receptor.

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GITR and GITR ligand play a role in immune cell signaling, activation, and survival. Here we present structures of human and mouse GITR bound to their cognate ligands. Human GITR–GITRL has potential to form a hexameric network, while murine complex forms a linear chain. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro assays and minimize higher order membrane structures in cell imaging experiments.

• ​NEW TALK - This Presentation Will be Given for the First Time

Specific requirements have to be met for the discovery of antibodies with challenging Target Product Profiles (TPPs). AbCheck has developed a technology to efficiently meet these requirements for e.g. functional antibodies or antibodies against targets with high homology. Our novel, tailored microfluidics technology is based on high throughput functional sorting of immune plasma cell repertoires at single cell level.

Recently introduced vaccines, based on lipid nanoparticles (LNPs) with encapsulated mRNA strands encoding the viral spike glycoprotein of SARS-CoV-2, have shown to be particularly effective in preventing COVID-19 infection. However, a drawback of the current mRNA-LNP COVID-19 vaccines is that they have to be stored at (ultra)low temperatures.  I will discuss proposed structures of mRNA-LNPs, factors that impact mRNA-LNP stability and strategies to optimize mRNA-LNP vaccine product stability.

• ​NEW TALK - This Presentation Will be Given for the First Time

Bispecific antibodies are often composed of multiple polypeptide chains, therefore the driving of correct quaternary assembly of these chains represents a major challenge to meet industrial scale productivity. Here we describe Chain Selectivity Assessment (CSA), a high-throughput method to rationally select parental mAbs to make bispecific antibodies. By deploying CSA, we have successfully identified mAbs that exhibit a native preference towards cognate chain pairing such that enables the production of classic Hetero-IgGs without additional engineering. Furthermore, CSA also identified rare LCs that permit positive binding of the non-cognate arm in the common LC Hetero-IgGs, also without engineering.