Acting fast: Two months to stop pandemic X from taking hold

Key to this undertaking are nucleic-acid-based technologies — those that are centered on DNA and RNA — including some developed under DARPA’s Autonomous Diagnostics to Enable Prevention and Therapeutics (ADEPT) program. Using these tools, scientists can identify protective antibodies from recovering patients and then, through a biological version of reverse engineering, manufacture genetic constructs that, when delivered, can instruct an individual’s body to produce similar protective antibodies. Significant quantities of these nucleic acid “blueprints” can be rapidly manufactured compared to state-of-the-art antibody production methods.

What is required now are breakthroughs in three other technology areas to bridge those past DARPA achievements and overcome the remaining bottlenecks that hinder rapid response to pandemic threats. The P3 program will pursue innovations in those three areas:

  • Growing virus needed to support evaluation of therapies in laboratory tests;
  • Subjecting antibodies to rapid rounds of evolution outside of the body to increase their potency beyond that of even the most effective antibodies obtained from infected patients; and
  • Developing means of efficiently delivering nucleic-acid-based protective treatments, since the technologies used to administer conventional vaccines do not readily translate.

Achieving and integrating breakthroughs in all of these areas will require choreographed cooperation among researchers and engineers specializing in such areas as immunology, microbiology, virology, medical infectious diseases, molecular biology, and medical countermeasure product development and manufacturing.

DARPA-funded teams will be required to demonstrate their integrated platforms in five simulations during the planned four-year program; they will initially test their platforms using pathogens of their choice, but ultimately they will test using DARPA-selected pathogens, including two demonstrations in which the identity of the pathogen will remain opaque to the teams until the 60-day clock starts. To ensure the developed platforms can produce a quality product with a viable pathway for regulatory review, each team will be required to complete a Phase I clinical safety trial before the end of the program.

A benefit of the nucleic-acid-based approach to limiting the spread of infection is that the genetic constructs introduced to the body would be processed quickly and would not integrate into an individual’s genome. Similarly, the antibodies produced in response to the treatment would only be present in the body for weeks to months. This is consistent with DARPA’s intent with P3, which is to safely deliver transient immunity to a virus, halting the spread of disease by creating a firewall.

“Our country asks our military Service members to deploy globally and provide humanitarian assistance in all manner of high-risk environments. We owe it to them to develop the best protections possible,” said Hepburn, a U.S. Army physician who previously served as Director of Medical Preparedness on the White House National Security Staff. “If we’re successful, DARPA could take viral infectious disease outbreaks off the table as a threat to U.S. troops and as a driver of global instability.”

To further clarify the P3 program vision, answer questions from potential proposers, and facilitate teaming, DARPA is hosting two identical Proposers Days. The first will be at the Crown Plaza Tysons Corner McLean Hotel in McLean, Virginia, on 22 February 2017, and the second at the Doubletree by Hilton Hotel San Diego Downtown in San Diego on 2 March 2017. Full details of the P3 program are included in a Broad Agency Announcement, available at: Proposal abstracts are due by 12:00 PM ET on 13 March 2017. Full proposals are due by 5:00 PM ET on 1 May 2017.

— Read more in Karuppiah Muthumani et al., “Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus,” Journal of Infectious Diseases (21 March 2016): 369-378 (DOI:; and “CureVac Receives Broad Patent for RNAntibody Technolog,” CureVac AG (8 November 2016)