Over the past several years, DARPA-funded researchers have pioneered RNA vaccine technology, a medical countermeasure against infectious diseases that uses coded genetic constructs to stimulate production of viral proteins in the body, which in turn can trigger a protective antibody response.

As a follow-on effort, DARPA funded research into genetic constructs that can directly stimulate production of antibodies in the body.1,2 DARPA is now launching the Pandemic Prevention Platform (P3) program, aimed at developing that foundational work into an entire system capable of halting the spread of any viral disease outbreak before it can escalate to pandemic status.

Such a capability would offer a stark contrast to the state of the art for developing and deploying traditional vaccines-a process that does not deliver treatments to patients until months, years, or even decades after a viral threat emerges.

"DARPA's goal is to create a technology platform that can place a protective treatment into health providers' hands within 60 days of a pathogen being identified, and have that treatment induce protection in patients within three days of administration. We need to be able to move at this speed considering how quickly outbreaks can get out of control," said Matt Hepburn, the P3 Program Manager. "The technology needs to work on any viral disease, whether it's one humans have faced before or not."

Recent outbreaks of viral infectious diseases such as Zika, H1N1 influenza, and Ebola have cast into sharp relief the inability of the global health system to rapidly contain the spread of a disease using existing tools and procedures.

State-of-the-art medical countermeasures typically take many months or even years to develop, produce, distribute, and administer. These solutions often arrive too late-if at all-and in quantities too small to respond to emerging threats. In contrast, the envisioned P3 platform would cut response time to weeks and stay within the window of relevance for containing an outbreak.

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, Va., on February 22, 2017, and the second at the Doubletree by Hilton Hotel San Diego Downtown in San Diego on March 2, 2017. For registration information, visit here.