COVID-19 Timeline: Diagnostics, Vaccines, and Therapeutic Antibody Development

1. Diagnostic development: The commercialization of the first COVID PCR test

• January 2020 – SARS-CoV-2 was cultured in the lab for the first time for the purposes of research. This was a critical early piece of the puzzle for the development of diagnostic tests and vaccines.
   
• February – March 2020 – Numerous genetic tests based on PCR, ELISA, and other techniques arose to meet the challenges of determining positive cases of viral infection and combating the spread of the disease.
   
• April 2020 – Eighteen Laboratory Developed Tests (LDTs) had achieved Emergency Use Authorization (EUA) from the FDA, a number that would double within one month.
   
• September 2020 – The number of EUA diagnostic tests reached in excess of 250, including over 200 molecular tests, 50 antibody tests, and multiple antigen-based tests. Such tests covered the lifecycle of viral infection from early detection of virus in the case of molecular and antigen tests, to immune responses measure by host antibody detection.

Process of diagnostic development using ELISA

The process of diagnostic development can involve multiple steps in identifying biomarkers indicative of virus. These include genetic signatures in the case of RT-PCR, or viral antigens in the case of antigen-based detection. Viral antigen and host antibody detection can be achieved by the use of enzyme-linked immunoassay (ELISA) and other quantitative approaches. Early characterization is paramount to understanding key targets for which tests and assays will eventually be developed.

The SpectraMax ABS and ABS Plus absorbance microplate readers provide the flexibility, sensitivity, and convenience for a wide range of assays such as ELISAs, microbial growth, and protein quantitation.

The SpectraMax® iD3 and iD5 Multi-Mode Microplate Readers measure absorbance, fluorescence, and luminescence. In addition, the iD5 reader measures TRF and FP and can be expanded to include TR-FRET, HTRF®, BRET, dual-luciferase reporter assays with injectors, and western blot detection.

The SpectraMax® i3x Multi-Mode Microplate Reader measures absorbance, fluorescence, and luminescence with available upgrades including western blot, cell imaging, and fast kinetics with injectors, plus additional detection modes.

The AquaMax® Microplate Washer is a fully self-contained system, configurable for both 96- and 384-well microplates.

On another front, a massive campaign was being waged in the development of vaccines to prevent SARS-CoV-2 infection and spread. Based on years of previous exploratory and preclinical work, several companies harnessed the genetic sequence of the virus in the creation of novel mRNA-based vaccines. Other routes of vaccine development were being explored as well, including those based on viral vector delivery systems and more traditional delivery of killed or attenuated viral particles. A multi-pronged approach was key to elucidating the most effective prevention strategies.

• April 2020 – Both Moderna and Pfizer had completed preclinical research and development of mRNA vaccine candidates. Johnson & Johnson and Astra Zeneca pursued clinical trials of their vaccine candidates in the ensuing weeks. These efforts were frontrunners in a wave of vaccine development, with over 80 vaccine candidates under development and at least five entering Phase 1 clinical testing around that time.
   
• April 2020 – The Moderna vaccine candidate reached a milestone by transitioning into the second round of dosing.
   
• May 2020 – Moderna received FDA clearance to advance into Phase II trials.
   
• June 2020 – The number of vaccines in development had climbed to over 130, with 16 in clinical trials.
   
• July 2020 – The Moderna Phase III clinical trial commenced.
   
• December 2020 – The Moderna vaccine was granted Emergency Use Authorization by the FDA, quickly followed by EUA approvals for the Pfizer BioNTech and Johnson & Johnson vaccines.
   
• May 2021 – The global community reached the major milestone of 1 billion COVID-19 vaccinations. This staggering accomplishment came a mere 4 months after vaccine rollout and just over a year after vaccine trials in humans began.

Solutions for antigen and immunogen discovery for vaccine development

Vaccine development hinges on the initial understanding of viral DNA, antigens, and immunogenic response by the host immune system. In vaccine research, immunogen assays are used in viral screens, followed by extensive characterization of positive immunogenic genes and proteins. These can then be engineered and optimized to facilitate downstream vaccine development efforts. Key steps in the process include the use of tools for screening and identification of positive cell clones.

In this video, Justin Dranschack, manager, BioPharma platform, reviews our workflow solution for vaccine development using recombinant proteins as the immunogen, and references the systems to aid in your research.

QPix® 400 Series Microbial Colony Pickers allow you to fully automate synthetic biology workflows for DNA assembly, antibody discovery, and protein engineering. With a variety of data tracking and assay tools, the QPix Software streamlines the control and management of complex and iterative processes.

The CloneSelect™ Single-Cell Printer™ (SCP) by Cytena and Molecular Devices is a fully automated system that utilizes proprietary microfluidics-based technology and real-time image analysis to sort and deposit single cells into standard microplates—while simultaneously providing assurance of monoclonality through image documentation.

The SpectraMax® i3x Multi-Mode Microplate Reader measures absorbance, fluorescence, and luminescence with available upgrades including western blot, cell imaging, and fast kinetics with injectors, plus additional detection modes.

Our ImageXpress High-content Imaging Systems offer an end-to-end solution for high-content screening and analysis. All our systems support a wide range of applications, increased throughput, and streamlined workflows.

3. Antibody discovery: The race to develop and scale therapeutic antibodies 

Although vaccine development efforts target the prevention of viral infection and spread, the advent of therapeutics to treat disease are equally important. The development of therapeutic monoclonal antibodies has played a critical role in bolstering the immune system and assisting patients afflicted with COVID-19. The process depends on identification and characterization of antibodies, protein engineering, and selection and growth of positive hybridoma cell lines.

• April 2020 – There were over 150 drugs under development for treating COVID-19, many of which had been previously approved for other viral infections and were indicated as safe for human use. At this time, according to the World Health Organization, there were over 1,000 ongoing clinical studies of treatments for COVID-19, many of which involved therapeutic antibodies.
   
• May 2020 – Phase II and III clinical trials were pursued for the novel fully human poly-clonal antibody therapeutic SAB-185, developed by SAB Biotherapeutics.
   
• July 2020 – Regeneron entered phase III clinical trials for a fully-humanized antibody cocktail REGN-COV2, containing two antibodies that bind non-competitively to the receptor binding domain of the virus’s spike (S) protein. This arrangement decreases the ability of mutant viruses to avoid treatment and protects against spike variants that have evolved in the human population.
   
• September 2020 – Data from the phase III trial for the REGN-COV2 antibody cocktail was shown to reduce viral loads and improve the systems of non-hospitalized COVID-19 patients.
   
• December 2020 – The FDA issued its first emergency use authorization for a COVID-19 antibody treatment. Bamlanivimab (from Eli Lilly) uses artificially engineered antibodies based on those isolated from people who have recovered from the disease, or convalescent patients.
   
• May 2021 – With FDA EUA approval for the novel antibody Sotrovimab, companies began designing next-generation antibodies modeled on those taken from unique individuals whose immune systems can neutralize SARS-CoV-2, including any novel variants that may arise.

Hybridoma generation and screening of large antibody libraries

Hybridoma technology is a method for mass-producing antibodies in a hybrid cell line generated from the fusion of antibody-producing B-cells with an immortalized myeloma cell line, called a hybridoma cell. Since every B-cell produces a unique antibody, single-cell cloning of hybridomas can be used to generate a diverse library of unique monoclonal antibodies at a large scale, which is frequently used in the prevention, diagnosis, and treatment of disease.

The video below presents our solution for a hybridoma workflow and references the systems to aid in your research.

The CloneSelect® Imager can help you meet regulatory demands of single cell verification with its automated analysis of cells in the white light channel and optional fluorescence to add another layer of confidence to monoclonality verification. The system also enables concurrent confluence and monoclonality studies.

The ClonePix® 2 Mammalian Colony Picker is a fully automated system for the selection of high-value clones used in antibody discovery and cell line development. Available with optional monoclonality assurance feature to condense cell line development workflows to a single instrument.

The SpectraMax® iD3 and iD5 Multi-Mode Microplate Readers measure absorbance, fluorescence, and luminescence. In addition, the iD5 reader measures TRF and FP and can be expanded to include TR-FRET, HTRF®, BRET, dual luciferase reporter assays with injectors, and western blot detection.

Our ImageXpress High-content Imaging Systems offer an end-to-end solution for high-content screening and analysis. All our systems support a wide range of applications, increased throughput, and streamlined workflows.

4. How to accelerate your COVID-19 research

Vaccine development workflows vary depending upon the platform (e.g., inactivated virus vs. DNA vaccine) chosen, each having its own advantages. To increase the likelihood of success against the infectious agent, CEPI, the Coalition for Epidemic Preparedness Innovations, and many other organizations promote diverse approaches during a pandemic.

We’ve created a variety of virus-related workflows – from antigen/immunogen and antibody discovery to stable cell line development. Above is a general workflow for vaccine development using recombinant proteins as the immunogen, referencing automated instrumentation to accelerate your research.

Learn more