Tag Archives: influenza

How to Prepare for Deadly Flu and Nuclear Fallout

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Breakthroughs in the science of programmable gene expression inspired DARPA to establish the PReemptive Expression of Protective Alleles and Response Elements (PREPARE) program with the goal of delivering powerful new defenses against public health and national security threats. DARPA has now selected five teams to develop a range of new medical interventions that temporarily and reversibly modulate the expression of protective genes to guard against acute threats from influenza and ionizing radiation, which could be encountered naturally, occupationally, or through a national security event.

The program builds from the understanding that the human body has innate defenses against many types of health threats, but that the body does not always activate these defenses quickly or robustly enough to block the worst damage. To augment existing physiological responses, PREPARE technologies would provide a programmable capability to up- or down-regulate gene expression on demand, providing timely, scalable defenses that are proportional to anticipated threats. Service members and first responders could administer these interventions prior to threat exposure or therapeutically after exposure to mitigate the risk of harm or death.

Influenza: “Researchers working within the PREPARE program seek to improve rates of survival and recovery in catastrophic scenarios for which reliable and scalable countermeasures don’t currently exist,” said Dr. Renee Wegrzyn, the PREPARE program manager….Three PREPARE teams are pursuing multi-pronged approaches to influenza defense and treatment that use programmable gene modulators to boost the human body’s natural defenses against influenza and also weaken the virus’ ability to cause harm by directly neutralizing the viral genomes. If successful, their approaches would potentially protect against virtually all influenza strains — regardless of whether a virus is newly emergent or has developed drug resistance — and would provide near instantaneous immunity, in contrast to traditional vaccines. Additionally, the teams are designing their countermeasures so that they are simple to deliver — for example, as intranasal sprays — reducing the logistical challenge of protecting large numbers of people.A team led by DNARx LLC, under principal investigator Dr. Robert Debs, aims to develop a new DNA-encoded gene therapy that helps patients fight influenza by boosting the natural immune response and other protective functions of their nasal passages and lungs.

Radiation Hazard Symbol

Ionizing Gamma Radiation: Other PREPARE teams are pursuing treatments to protect the body from the effects of ionizing gamma radiation. In humans, radiation poisoning primarily affects stem cells in the blood and gut, yet existing treatments only help to regenerate blood cells, and only with limited effect. There is no possibility for prophylactic administration of these drugs, and most must be delivered immediately following radiation exposure to provide any benefit. There are no existing medical countermeasures for radiation damage to the gut…
A team led by the University of California, San Francisco, under principal investigator Dr. Jonathan Weissman, also aims to develop gene therapies to enhance resilience against ionizing radiation. The team’s approach should result in an intravenous or orally available treatment that activates innate defenses in gut and blood stem cells for a period of several weeks.

A Dose of Inner Strength to Survive and Recover from Potentially Lethal Health Threats
New tools for programmable modulation of gene expression could yield enhanced resilience against influenza and ionizing radiation for service members and first responders, DARPA Press Release, June 27, 2019

The Next Pandemic and the US Military

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U.S. military forces are the front line of U.S. national security, but as a globally deployed force they are also on the front line of any new pathogen-based health threat that may emerge [including also due to biological warfare]. As overall human activity pushes ever further into previously undeveloped territory, the likelihood of exposure to new pandemic diseases increases.  The 2009 Army Posture Statement, cites a World Health Organization estimate of between 20 and 50 percent of the world’s population being affected if a pandemic were to emerge. WHO forecasts “it may be six to nine months before a vaccine for a pandemic virus strain becomes available.” In a separate report on pandemic influenza, the WHO describes several challenges to producing sufficient volumes of vaccine using current, egg-based protein-production technology, including the likelihood that two doses per person could be required due to the absence of pre-existing immunity.

In short, the potential for a pandemic exists and current technological limitations on defensive measures put the health and readiness of U.S. military forces at risk. A technological solution to increase the speed and adaptability of vaccine production is urgently needed to match the broad biological threat.

DARPA’s Blue Angel program seeks to demonstrate a flexible and agile capability for the Department of Defense to rapidly react to and neutralize any natural or intentional pandemic disease. Building on a previous DARPA program, Accelerated Manufacture of Pharmaceuticals, Blue Angel targets new ways of producing large amounts of high-quality, vaccine-grade protein in less than three months in response to emerging and novel biological threats. One of the research avenues explores plant-made proteins for candidate vaccine production.“Vaccinating susceptible populations during the initial stage of a pandemic is critical to containment,” said Dr. Alan Magill, DARPA program manager. “We’re looking at plant-based solutions to vaccine production as a more rapid and efficient alternative to the standard egg-based technologies, and the research is very promising.”

In a recent milestone development under Blue Angel, researchers at Medicago Inc. produced more than 10 million doses (as defined in an animal model) of an H1N1 influenza vaccine candidate based on virus-like particles (VLP) in one month….“The results we’ve achieved here with plant-based production of vaccines represent both significant increase in scale and decrease in time-to-production over previous production capabilities in the same time period. The plant-made community is now better positioned to continue development and target FDA approval of candidate vaccines,” Magill said. “Once the FDA has approved a plant-made vaccine candidate, the shorter production times of plant-made pharmaceuticals should allow DoD to be much better prepared to face whatever pandemic next emerges.”

DARPA Makes 10 Million Strides in the Race to Contain a Hypothetical Pandemic, July 25, 2012