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Designing a smarter vaccine for the coronavirus

Local biotech firm Epivax seeks to apply its expertise to develop a computational plan of attack

Photo by Richard Asinof

The sign above the reception desk at EpiVax in Providence, where the firm's potential work in designing a smarter vaccine for the coronavirus is very much part of the mission: fearless science.

By Richard Asinof
Posted 2/10/20
The local biotech firm, EpiVax, is poised to play a critical role in helping to design a smarter vaccine to fight the coronavirus.
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In the soon-to-be released RI Innovates 2.0 report, EpiVax was found to be the leading non-hospital entity in receiving NIH research grants between 2016-2019, with more than $14 million in awards.

PROVIDENCE – The rapid spread of the novel coronavirus has created a world health emergency and mobilized efforts to create a rapid response vaccine by a number of private and government entities.

As of this weekend, the rate of infections and the number of deaths have now exceeded the SARS virus, as China attempted to isolate and quarantine its population around the Wuhan province in order to contain the deadly spread of the virus, which has sickened more than 30,000 people, with a rising number of fatalities.

As the headline in a recent Washington Post story said, describing the efforts to develop a vaccine: “Coronavirus vaccine research is moving at record speed,” adding, “The science is fast, but the virus is faster.”

Traditional vaccine development efforts have usually taken decades, not months, according to Barney Graham, the deputy director of the Vaccine Research Center at the National Institutes of Health hopes to have a vaccine in human testing by April, according to the story written by Washington Post reporter Carolyn Johnson.

At EpiVax, a local biotech firm that recently celebrated its 21st year in business, Lenny Moise, Ph.D., the Director of Vaccine Research at the firm, is in charge of developing a plan of action for potential funders, including the National Institutes of Health and the global Coalition for Epidemic Preparedness Innovations, to design a vaccine that not only maximizes the ability to attack the coronavirus spike protein but also minimizes the potential for the vaccine to induce immune responses that supprss vaccine efficacy.

EpiVax's previous work in designing a smarter vaccine for the H7N9 flu, using its proprietary immuno-informatics technology, positions the firm to play a critical role in the collaborative research efforts for a corona virus vaccine, taking a similar approach.

Here is the ConvergenceRI interview with Lenny Moise, the Director of Vaccine Research at EpiVax, detailing the efforts that are now underway.

ConvergenceRI: What is EpiVax’s approach to designing a vaccine for the coronavirus?
MOISE:
We have unique tools that allow us to probe the virus’s ability to evade immunity and for the immune system to target the virus. We are in a great position to be able to say something about the potential for the virus to escape immune responses, and we have the ability to see if people have pre-existing immunity to related viruses that we can take advantage of in order to beat this virus.

ConvergenceRI: A recent news story quoted Dr. Annie De Groot, the CEO and CSO of EpiVax, that you are in conversations with potential funders and partners for this work. Can you talk about that work, or is it still in gestation?
MOISE:
We are still in the early stages, and I don’t think we can identify the different partners right now, but we’re [exploring] different strategies to produce a vaccine.

Our major consideration is [to be able] to fund the work.

The U.S. government has made it clear that they are funding proven technologies or technologies that are on the cusp of licensure, so we’re talking about vaccine platforms that have a good track record in terms of safety and efficacy.

ConvergenceRI: How has your previous work on the H7N9 flu informed your current work?
MOISE:
The work that we have done with H7N9 is one approach that we can take here.

We expect the antibody response will target a surface protein called Spike on the coronavirus. Spike attaches the virus to cells, allowing the virus to fuse with the cell membrane and release its genetic material into the cell in order to begin replication, which will lead to the viral spread, disease, and eventually transmission.

We expect that many vaccine developers will target that protein, because an antibody response that neutralizes Spike will prevent infection.

The ideas that we have about Spike involve evaluating its ability to stimulate a T-cell response that supports the antibody response. The T-cell response is critical for an antibody response. If the antigen doesn’t have high enough quality T-cell triggers, then the antibody response will not be effective, as we saw with H7N9 flu.

If Spike has a high T-cell epitope content, that would be a good sign. But there could also be human-like T-cell epitopes that could activate suppressive mechanisms that would limit the T-cell response and make the vaccine less effective.

We have designed ways of removing epitopes like that to make a Spike vaccine more effective.

ConvergenceRI: What are the stumbling blocks to moving ahead. Is it finding the funding to do this work?
MOISE:
It’s the funding, because while we can design a vaccine, it doesn’t mean that we can produce it and test it. It requires significant funding make that to make that possible.

It also involves developing an animal model that will reliably replicate the disease that is observed in humans.

ConvergenceRI: Would that be a mouse model?
MOISE:
It could be a mouse model or it could be non-human primates.

If we use SARS as an example, non-human primates do not become very ill when infected with SARS.

On the other hand, mice are not naturally infected by SARS but the virus was adapted for mouse infection. The mouse-adapted virus did make mice very ill, which made it feasible to test vaccines for SARS. That could be the case here as well.

The novel coronavirus binds the same receptor on human cells as SARS, a protein called ACE 2.

ConvergenceRI: How involved has the U.S. government been in speeding vaccine design work for the coronavirus?
MOISE:
The government is making a concerted effort to develop medical counter measures against the novel coronavirus.

It set up a task force that includes BARDA, the FDA, CDC, and NIH to coordinate efforts to develop these counter measures, with BARDA [the Biomedical Advanced Research and Development Authority] serving as the clearinghouse for any ideas for rapid development. Ideas that people have for funding work that will lead to rapid development of counter measures, be they vaccines or therapeutics, will go through BARDA.

There is a task force that was organized that includes  with BARDA serving as the clearinghouse for ideas for rapid development.

NIH is also recommending that people who have grants should apply for administrative supplements; that’s something we can do, because we have an active NIH grant.

The federal government has not yet announced how much it is dedicating to this effort and whether it is diverting funds from other areas to move the research forward for the response to novel coronavirus,

ConvergenceRI: Dr. De Groot recently became affiliated with the University of Georgia. What kinds of resources would be available for your potential work on the design of a coronavirus vaccine?
MOISE:
The University of Georgia has excellent resources for putting together all the different components of a vaccine development project to address the 2019 novel coronavirus.

It has experts and facilities to do that work There are infectious disease experts , animal model experts; there is biosafety Level 3 animal research facility, which will enable testing of vaccines, and development of animal models to understand the course of the disease and infection.

ConverenceRI: It seems that EpiVax is in unique position with its immuno-informatics technology to be able to design and tweak the vaccine on both sides of the equation, both in terms of the antigen, but also with the immune response, the way that the virus may evade the immune response. Did I say that correctly?
MOISE:
Yes, we are able to deisgn an antigen to maximize its immunogenicity potential and to minimize its ability to suppress immune responses that reduce vaccine efficacy.

ConvergenceRI: What are the next steps?
MOISE:
The vaccine strategy is solidifying. We’ve spoken to many different groups that have different expertise needed to design, produce and test vaccines. Those parts are coming together.

Now it’s time to put a coherent and credible plan together on paper and to propose that to NIH.

ConvergencRI: So, you are tasked with writing that proposal? That’s no small task.
MOISE:
That’s right. I want to do it. It is exciting. It is an opportunity to make an impact.

Plersonally, I would prefer seeing this coronavirus peter out.

But if it doesn’t, we need to have a response that is effective. Even if we don’t make a vaccine that will be tested in the next three months in clinical trials, we will be at least well on our way to designing a smarter vaccine, not just designing a vaccine.

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