The current COVID-19 pandemic has demonstrated how quickly an emerging infectious disease (EID) can spread across the globe, threaten individual heath and wreak havoc on the economy and our way of lives.

Almost a decade before the current COVID-19 outbreak, Mass General investigator and Infectious Diseases Physician, Mark Poznansky, MD, PhD, received funding from the Defense Advanced Research Projects Agency (DARPA) to develop a platform for accelerated vaccine development in the event of a rapidly spreading EID.

That forward-thinking funding resulted in the creation of the VaxCelerate Consortium, a platform capable of generating and clinically testing a new vaccine in less than 120 days.

Dr. Poznansky, director of the Vaccine and Immunotherapy Center (VIC) and a Steve and Deborah Gorlin MGH Research Scholar 2015-2020, is now using that platform (which he co-invented with Dr. Jeffrey Gelfand, Infectious Diseases Physician and Senior Scientist at VIC), to rapidly develop and test a vaccine for COVID-19.

The VIC team hopes to start testing a vaccine in laboratory models by the middle of this month.

Accelerating the Process

A key challenge in developing vaccines for emerging infectious diseases is that each pathogen uses a different mechanism to infect cells and elicits a different immune response from the body. The majority of vaccines are built from ground up to address these unique factors and need to undergo rigorous efficacy and safety testing—a process that can typically take up to six years.

As the name suggests, VaxCelerate is designed to speed up the development of new vaccines. It consists of two components that can both be manufactured rapidly:

• A base that activates the immune system and is very stable and can be stockpiled—in this case, the base is a protein that evokes a broad antiviral immune response to anything attached to it
• A spearhead that can be rapidly generated to help to direct this response—peptides and small proteins unique to the virus that are identified through a computational analysis of the viral genome

The base and the spearhead are attached by two molecules that act as a biological glue and connect them “like Legos” when mixed in a simple solution, Poznansky explains.

For SARS-COV-2, the VIC already has a stock of the base in house and has identified peptides from the virus’ genome to target with the vaccine. This will be the team’s third time working to go from genome to vaccine, having previously displayed proof of concept with the Lassa Fever virus.

“We don’t have to re-invent the wheel, we just have to turn it,” Poznansky explains. “This time we’re turning it in a live fire test.”

A Forward-Thinking Collaborative Effort

Poznansky credits the United States Department of Defense—and DARPA in particular—for their forward-thinking view on pandemic preparedness.

“This is a collaboration of the U.S. government, philanthropy and industry,” he says. “We would never have been able to do it without the DOD initiating this project, philanthropy bridging and supporting advances in the overall platform, and industry funding and guiding its development as a potentially important vaccine product.”

“There were times when we wanted to push the system, but the DOD funding had narrower objectives. Philanthropy allowed us to stretch the technology, broaden its capabilities, and apply it to other targets such as cancer vaccines.”

The biotech industry is playing a crucial role as well. Six months before the COVID pandemic, a company called Voltron Therapeutics licensed the VaxCelerate technology from VIC at MGH.

When the pandemic hit, the company formed a joint venture with Hoth Therapeutics (HaloVax) and initiated a sponsored research agreement with VIC to develop the vaccine. “Two weeks after the alarm bells were ringing in the US, we were up and running, building a vaccine in partnership with a company,” he says.

“The pandemic has surpassed any normal approach to dealing with a disease where you could say, ‘Well, we have time. We’ll work it out.’ The need is so overwhelming based on what we’re seeing at Mass General and beyond.”

What Success Could Look Like

Given the pressing need for tools to reduce the devastating impacts of COVID-19, a successful vaccine may not have to be perfect, Poznansky says.

“Obviously, we want to prevent everybody from getting the disease. But if we could prevent high-risk individuals from getting infected and developing the most serious consequences through vaccination, that would be very important.”

COVID-19 Research at Mass General
Researchers and clinicians at Massachusetts General Hospital Research Institute are mobilizing to develop new strategies to diagnose, treat and prevent COVID-19. Learn more.