Traditional hybridoma and phage display methods have failed to yield therapeutic antibodies against difficult targets like most GPCRs and ion channels. This presentation will introduce Berkeley Lights’ new Opto™ Plasma B Discovery 4.0 workflow that enables recovery of 1000s of hits by screening up to 100,000 plasma B cells, down-selection of lead candidates by functional screening, and sequencing and re-expression of >1000 functionally-characterized antibodies … all in just 1 week. By maximizing the diversity of antibodies through direct functional profiling of plasma B cells, the Opto Plasma B Discovery 4.0 workflow will allow users to tackle even the most challenging targets.

From understanding basic mechanisms of how various SARS-CoV-2 proteins function to discovering new molecules that can interact and potentially inhibit various viral protein targets, we provide an overview of how artificial intelligence methods are being used to study COVID-19. We provide an overview of some of these AI methods and how they have enabled novel insight into the function of SARS-CoV-2 proteins.

Accelerated development almost by definition means going out of your comfort zone. A case study on our lab's pivot to support the NIH COVID19 Serosurvey by providing recombinant SARS-CoV-2 proteins will be presented. The balance between speed, efficiency, and productivity is fraught with decisions that often have little supporting data. Nevertheless, general lessons learned in the past are critically important.

Warnings from the scientific community around the impact of a global pandemic have largely gone unheeded, despite several recent outbreaks, including pandemic influenza, SARS and MERS.  Even continual Ebola outbreaks in sub-Saharan Africa failed to capture sufficient global attend to ensure globally coordinated pandemic readiness. This has now shifted with the emergence of COVID-19 and while we are still in the early phase of this pandemic, it has impacted every corner of the globe and changed life as we know it.Since Jan 2020, working alongside CEPI and a team of Australian and International collaborators, the UQ team shifted its Molecular Clamp rapid response program to development of a vaccine candidate for COVID-19.  We have moved rapidly through pre-clinical testing and are currently completing early phase clinical studies.  We have also partnered with CSL, who are currently advancing both large-scale manufacturing and pivotal stage clinical development for widespread distribution and use. 

Sorrento Therapeutics acquired SmartPharm, a gene-encoded therapeutics company developing non-viral DNA and RNA gene delivery platform. Through this collaboration/acquisitions Sorrento has identified STI-2020dna (DNA plasmid injection), an antibody encoded DNA plasmid candidate derived from Sorrento’s proprietary STI-1499 (COVI-GUARD™). STI-2020dna has generated antibodies in vivo directed against the SARS-CoV-2 virus, including  D614G-bearing virus isolates. STI-2020dna is currently under development with the potential to generate long-lasting anti-viral protection with a single intra-muscular administration.

The global SARS-CoV-2 pandemic has challenged healthcare systems around the world even after almost a year of efforts to contain spread and treat patients. One of the brightest spots has been the record pace of scientific and medical discoveries that have led to generation of promising vaccines and antibody therapeutic against SARS-CoV-2 centered on Spike protein (S). ACROBiosystems is proud to support development of vaccines and therapeutics against COVID-19.

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. Here, it is shown that rapid conversion of recombinant RBD into particulate form via admixing with liposomes containing cobalt-porphyrin-phospholipid (CoPoP) potently enhances the functional antibody response. These results confirm that adjuvant and presentation strategies can help induce strongly neutralizing antibody responses against SARS-CoV-2.

COVID-19 therapeutics directed against SARS CoV-2 proteins, particularly the SARS CoV-2 spike protein, is actively being pursued.  We are developing single domain antibodies (heavy chain-only antibodies or nanobodies) from alpacas that block the attachment of SARS-CoV-2 to human target cells, and thus provide passive immunity against the virus. These small, yet highly specific nanobodies have previously shown promise in treating other viral infections, and thus represent a promising strategy for generating useful anti-SARS-CoV-2 therapeutics. We have produced a library of nanobodies directed against the SARS-CoV-2 spike protein (S protein) and its receptor-binding domain (RBD). We are in the process of identifying anti-spike nanobodies that act as neutralizing nanobodies by blocking the binding of the virus to its cellular receptor, angiotensin converting enzyme-2 (ACE2). The most effective nanobodies will be explored for their action as passive immunity agents and the ability to deliver these nanobodies through nasal delivery.

The speed and flexibility of peptide synthesis is a major advantage when handling rapidly evolving conditions, such as SARS-CoV-2 infection and vaccine development. These applications demand high peptide purity and yield, and the ability to quickly synthesize many peptides in parallel for timely treatment. Here we present examples of how peptide-based epitopes and therapeutics are synthesized for COVID-19 and neoantigen applications.

The spike proteins S of SARS-associated coronaviruses bind with moderate affinity to ACE2 on host cells as an entry receptor. Guided by deep mutagenesis, ACE2 was engineered as a high affinity soluble decoy that blocks receptor-binding sites on S of SARS-CoV-2 and related betacoronaviruses.  The engineered decoys potently neutralize infection with an efficacy that rivals affinity-matured monoclonal antibodies.

We will present a modular method to produce Antibody-Like Nanodiscs (ANL). Using our method, we have created and tested ANL against SARS-CoV-2 infection. The method for making these ANL as well as the neutralization of SARS-CoV-2 data will be presented and discussed.