AstraZeneca, the transformative Big Biotech business, steered from Cambridge UK, has joined forces with government and academia in an historic global alliance designed to discover novel coronavirus-neutralising antibodies.

Harnessing internal expertise and via new collaborations, the vision is to identify monoclonal antibodies that have the potential to recognise, bind to and neutralise the SARS-CoV-2 virus and slow the impact of COVID-19.

More than 50 virology, protein engineering, clinical and bioprocess experts across BioPharmaceuticals R & D and Operations are working on this effort, using proprietary antibody discovery technology that was previously developed under an agreement with the US Defense Advanced Research Projects Agency (DARPA) as part of the Pandemic Preparedness Platform programme. 

As part of the DARPA programme, the technology enabled AstraZeneca scientists to rapidly discover potential therapeutic antibodies for influenza-A in less than 60 days.

AstraZeneca executive Mene Pangalos says: “Through our scientific expertise in infectious disease and antibody discovery and development, we have rapidly mobilised our research efforts to help respond to the COVID-19 global pandemic.

“By partnering with government and academia, our ambition is to accelerate the discovery and development of a safe and effective antibody treatment to help fight COVID-19.”

AZ’s technology can capture and screen antibodies from millions of primary B cells. The company is also utilising hybridoma technology, which is a method for producing large numbers of monoclonal antibodies through a culture of hybrid cells that results from the fusion of B cells and immortal myeloma cells.

Once identified, the monoclonal antibodies are screened against their ability to bind to the spike protein before further developability tests are carried out.  AstraZeneca is aiming for clinical evaluation in the next three to five months.

The international collaborative efforts are designed to evaluate additional promising candidates for future clinical use.

The Chinese Academy of Sciences and Vanderbilt University Medical Center in the US are providing AstraZeneca with genetic sequences for antibodies they have discovered against SARS-CoV-2 for further in silico and in vitro assessment.

Via collaborations with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) and the University of Maryland School of Medicine, promising antibodies from AstraZeneca – discovered through its internal research efforts and collaborations – will undergo preclinical safety and efficacy assessment in the organisations’ biosafety level 3 (BSL3) laboratories.

The company is also in discussion with world governments to support clinical development and manufacturing capabilities.

There are currently no specific treatments for COVID-19. Researchers across the world, including AstraZeneca, are investigating preventative approaches and treatment options for COVID-19, including monoclonal antibodies, vaccines and antivirals, as well as investigating the repurposing of existing drugs to treat the infection.  

A vaccine is a prophylaxis, or preventative, approach against disease. Vaccines require an immunisation and a healthy immune system; they have the potential to provide long-term protection against the virus, though it is estimated that it could take at least a year before a vaccine against COVID-19 is approved.

Monoclonal antibodies synthesised in the laboratory mimic natural antibodies. It is hoped that an antibody-based treatment could neutralise the SARS-CoV-2 virus and thus, in theory, be given as a preventative option for those exposed to the virus, as well as treat and prevent disease progression in patients already infected by the virus. An antibody-based treatment has the potential to provide immediate effect in the patient.

Mene Pangalos added: “At AstraZeneca we have a long history of and deep expertise in discovering and developing antibody-based treatments for a range of diseases.

“The proprietary technology we are using to identify novel coronavirus-neutralising antibodies has already been pressure-tested against influenza-A in response to the DARPA P3 programme. 

“Harnessing these capabilities, our scientists are working tirelessly and collaboratively, hoping we can contribute to putting an end to this crisis as fast as we can.”

AstraZeneca scientists are exploring three potential sources for antibodies against the SARS CoV-2 virus – patients who have recovered from COVID-19, immunised humanised mice and laboratory techniques such as phage display.

The spike protein on the SARS-CoV-2 virus is the primary target being explored for potential COVID-19 monoclonal antibodies. The aim is that by targeting the spike protein, the antibody will be able to neutralise the SARS-CoV-2 virus and affect its capacity to infect healthy cells.