Prompted by the launch of Sputnik in 1957 by the Soviet Union, the U.S. Department of Defense (DoD) a year later established DARPA—the Defense Advanced Research Projects Agency—to support a robust and agile technology program dedicated to U.S. national security. In the coming decades, DARPA would contribute to developing GPS, the internet, and other critical technological advancements, including most recently a vaccine for COVID-19.
As a growing number of infectious diseases—Ebola, Zika, and others—increasingly highlighted both the global threat as well as the lack of a public health response, DARPA launched the Pandemic Prevention Platform (P3) program in 2017. As part of DARPA’s mission to support U.S. military readiness, the P3 program sought to protect DoD personnel deployed around the world and at risk for highly contagious infectious diseases.
With the objective of containing an outbreak and halting the spread of an infectious disease before it becomes a pandemic, the P3 program focused on ways to dramatically accelerate the development of preventive medical countermeasures, specifically monoclonal antibodies (mAbs). Their goal was to develop a scalable, adaptable, and rapid response platform capable of producing the necessary doses against any known or unknown infectious threat within 60 days. Compared with the four to 10 years typically required to develop antibody therapeutics, this time frame was viewed as highly ambitious, even audacious.
As part of the P3 program, research teams at AbCellera Biologics, AstraZeneca, Duke University, and Vanderbilt University began studying how to most rapidly identify antibodies that would be effective against an infectious virus, as well as ways to deliver the genetic code for producing these protective antibodies so that host human cells could follow the “instructions” and produce the antibodies themselves.
This gene- encoded antibody approach had the advantages of being easily manufactured at scale using largely synthetic processes, transported and stored without many of the cold-chain logistics required by traditional medical countermeasures, delivered with near-immediate efficacy, and safely expressed in the body for only a limited duration, causing no permanent alteration to an individual genome.
P3 research initially targeted a wide range of infectious diseases; however, the teams quickly shifted their focus to developing antibody therapeutics and prophylactics for the novel coronavirus when it was first reported in China in 2019. AbCellera Biologics, a Vancouver-based technology company, obtained a sample of blood from a recovering U.S. patient at the end of February 2020 and studied potential antibody candidates after testing them to see how well the mAbs bound to and neutralized the virus.
Among thousands of anti-SARS-CoV-2 antibodies identified by AbCellera Biologics, bamlanivimab (LY-CoV555) was identified as the lead candidate and selected to enter human clinical trials in North America. In May, AbCellera Biologics started working with Eli Lilly on the large-scale manufacturing of this mAb therapy to target the SARS-CoV-2 virus. In November 2020, the U.S. Food and Drug Administration granted emergency- use authorization.
Bamlanivimab (administered on its own as well as in combination with other antibodies) has treated at least 700,000 patients and prevented COVID-19-related hospitalizations and deaths. In addition, bamlanivimab reduced by up to 80 percent the risk of contracting symptomatic COVID-19 among residents and staff of long-term care facilities.
Bamlanivimab was just the first of several success stories for the research teams funded
by the P3 program. Another antibody product—a cocktail of two antibodies discovered by Vanderbilt University—was licensed to fellow P3 team AstraZeneca and received Emergency
Use Authorization in December 2021 for pre-exposure prophylaxis among individuals at high
risk of contracting severe COVID-19 disease. A team at Duke University also discovered several highly potent SARS-CoV-2 antibodies and is planning a clinical study of an RNA-encoded version of their leading candidate. In addition, AbCellera Biologics and partner Eli
Lilly developed a second antibody, bebtelovimab, against the most common and fastest- spreading Omicron variants; bebtelovimab received Emergency Use Authorization in February 2022 for use in high-risk individuals.
The development of multiple COVID-19 medical countermeasures by the P3 program shares similarities with other past ground-breaking achievements of DARPA. By taking a transformative—not incremental—approach, the P3 program succeeded in developing a breakthrough technology with impressive speed. Its bold vision also reflected a far- sightedness that saved countless lives. By investing early on in the P3 program, DARPA once again fulfilled its mission of protecting U.S. national security.
For more information, see:
Nature, Jan. 12, 2021: How COVID Unlocked the Power of RNA Vaccines
The Washington Post, July 30, 2022: How a Secretive Pentagon Agency Seeded the Ground for a Rapid Coronavirus Cure