Innovation Ecosystem

EpiVax at the epicenter

Dr. Anne De Groot talks about the emergence of her firm and its immuno-informatic tools

PHOTO BY Scott Kingsley

The immuno-informatic tools developed by Dr. Anne S. De Groot and her team at EpiVax are beginning to gain traction in the development of vaccines with greater efficacy.

By Richard Asinof
Posted 7/21/14
Dr. Anne S. De Groot is one of the key movers and shakers in the global vaccine world. Her firm, EpiVax, has developed new computational tools to lead in the development of improved, personalized vaccines.
Agencies such as BARDA have begun to engage with De Groot and her team, which could lead to exciting new developments in improving the efficacy of flu vaccines.
From her leadership at the Clinica Esperanza to her directing of iCubed, De Groot has invested her energy in developing a new vision for Rhode Island’s future.

When De Groot talks, our federal delegation listens and pays attention; why is that not the case with the R.I. General Assembly and CommerceRI? What kinds of investment by federal agencies will it take to move toward adoption of the new tools developed by De Groot and her team at EpiVax? As the next governor maps out the future economic development map for Rhode Island, what role will the emerging biotech industry play? Will it be seen as a catalyst for economic growth? How can the work being done by Clinica Esperanza be incorporated into a new model of health care delivery in Rhode Island?
The spread of viruses across continents and oceans as the temperatures keep rising translates into increased health and security risks across the world. The health costs of climate change are almost never factored into the economic equation of resiliency, which all too often focuses on preserving coastlines and protecting property – without addressing any of the root causes.
The immuno-informatic tools developed by EpiVax can play an important role in protecting our national health security – and improving the efficacy of vaccines.
We have seen the rise in whopping cough and measles as a result of vaccine-deniers, who sound all too similar to those climate change deniers in their tone and rhetoric.

PROVIDENCE – Dr. Anne S. De Groot seems to be a verb, to borrow a phrase from R. Buckminster Fuller. She is a force constantly in motion, at the center of a whirlwind of activities, ideas and collaborations, at the nexus of Rhode Island’s innovation ecosystem – and beyond.

De Groot, the CEO and chief science officer at EpiVax, is at the forefront of global efforts to create and apply computational biotech tools to address immune system disorders worldwide – from H7N9 flu to animal viruses to the threat from Ebola.

Companies in Japan are now using her company’s technology to manufacture vaccines, and the U.S. government is beginning to engage with her about using the tools EpiVax has developed to create greater efficacy in flu vaccines.

The longer-term goal is to usher in a new world of personalized vaccines, tailored to each individual’s genomic makeup, following an innovative genome-to-vaccine approach.

At the other end of the health innovation spectrum, De Groot is the founder and a clinician at the Clinica Esperanza/Hope Clinic, which provides free, high-quality medical care to about 2,000 uninsured adults living in Rhode Island. She is passionate about the need for greater community equity in health care and in the promotion of prevention and a healthier lifestyle.

De Groot also directs the Institute of Immunology and Informatics, or iCubed, at the University of Rhode Island, which will host the eighth annual national Vaccine Renaissance Conference on Oct. 13-16 in Providence.

ConvergenceRI sat down to talk with De Groot recently at her office on Clifford Street, in the heart of what some now call the Knowledge District. EpiVax has hired five new employees since January, a sign of the increasing traction that the firm has gained.

ConvergenceRI: Where is EpiVax now with its work on H7N9 flu?
DE GROOT:
Last year at this time we were coming off the initial wave of the H7N9 epidemic. We have [put in] two years of work on H7N9. And, it had re-emerged in October and November.

We predicted that there would be low immunogenicity in May of 2013, based on our immuno-informatic analysis. And, we got, in one day, 5,000 hits on our website. People were very, very, very interested in that.

It was a complete prediction; let’s go way out a limb and say something that is purely based on computational immunology.

Then everyone goes: What’s the evidence?

Well, the evidence is now in. Two companies made vaccines, and they produced them in a very short period of time; that was really excellent. One of them was Novartis, and they produced [the vaccine] using proteins in cell cultures, instead of using eggs.

They did a standard vaccine study. They immunized I think a couple hundred patients.

One arm of the study group just got the standard flu vaccine, with no adjuvant. The other group got an adjuvant vaccine – because they knew, because we told them, it was going to be low [in immunogenicity].

The adjuvant vaccine worked; if you look at the press release by Novartis, there was an 80 percent conversion to [an immune response to] the H7N9 flu virus.

But, if you read the fine print, you’ll see that the pure vaccine, without adjuvant, only converted between 9 and 16 percent of the patients, which is the lowest ever.

This is really very dramatic; [it shows that] there is a lack of T-cell response, a lack of antibody responses, and that’s what they demonstrated in this clinical trial of the vaccine.

To me, that’s proof in the pudding. That’s the validation we needed. We predicted, and then we validated. So, we didn’t have to do the clinical trial [ourselves], [Novartis] did the clinical trial. [See link to ConvergenceRI story below.]

ConvergenceRI: What happened next?
DE GROOT:
And wait, there’s more. Hopefully, we’ll have a paper coming out soon, we’re putting the final touches on it now, showing that part of this virus actually induces what we call regulatory [resistance]. So, rather than stimulating an immune response and creating inflammation that allows [your body] to respond, the virus has found ways to trigger a suppressive immune response.

It’s incredibly important for vaccine design, because it is relevant to other viruses as well.

Some viruses change their sequences to look like you – they don’t just change their sequences, they change the sequences that would stimulate immune response, and the sequences that would normally regulate immune response. They actively suppress immune responses.

One of these viruses is herpes. It’s been impossible to make a herpes vaccine; people have tried and failed, tried and failed, and tried and failed. They’ve tried everything – sub-unit viruses, sub-unit proteins; they’ve tried this protein, they’ve tried that protein.

Sixty percent of people in the world have Herpes Simplex Virus, or HSV; it’s something that people don’t like to have [because of the sores]; it would be a great market for which to make a vaccine.

Why have we failed to make a vaccine? Because, we hypothesize, that the virus has evolved in our bodies and changed its immune response to induce regulatory [immune suppression].

That’s a huge discovery. I have said, and I believe that it’s true, that the tools we’ve developed to predict this, is more important than Tregitope [discovered by EpiVax in 2008], and we’ve been talking about Tregitope for years.

I’m [saying] that viruses and bacteria and parasites, they all make these Tregitopes [to suppress immune responses and inflammation.]

The reason that we have failed to make [successful] vaccines [for viruses such as herpes] is because we’ve failed to recognize that. It’s a fundamental immunology discovery; it’s a fundamental vaccine discovery. It will completely change the way we make vaccines. And we have it; we invented it here.

ConvergenceRI: How will get this to the market?
DE GROOT:
People are excited about it. In Japan, clients that we are working with are making vaccines for chronic infections from viruses; they are using our tools.

Another problem with vaccines is that, over the years – and I don’t want to knock vaccines – but some vaccines may induce an adverse immune response.

[In response to the California strain of the H1N1 flu and the vaccine,] some people developed narcolepsy. When you have it, you definitely notice it; you fall asleep in the middle of the day, when you’re driving, you fall asleep. People go to their physician for that.

After the flu epidemic in 2009, there was an outburst of [narcolepsy] cases in China, in California, in Finland and in Sweden.

In Finland and Sweden, they actually track vaccinations, and they have a national program, and everyone gets the same vaccines. They got the adjuvant H1N1 California vaccine.

And they found that the vaccine resulted in narcolepsy in kids, not so much adults, but kids with a certain genetic disposition. They started having much more narcolepsy than before, and because they tracked all those cases, they found a significant increase in the number of cases of narcolepsy following vaccination.

They traced it back to a single epitope presented by patients, similar to the flu virus protein. When you have an immune response to the virus, you make T-cells that kill neurons in your brain, and those neurons were responsible for keeping you awake.

ConvergenceRI: Given all the fears about emerging viruses, such as MERS and Ebola, one would think that government agencies would be knocking at your door, to learn how to use these tools.
DE GROOT:
I think that they thought that they could solve the problem by throwing money at it.

Because of the failure of the flu response in 2009, the U.S. government turned to BARDA [the Biomedical Advanced Research and Development Authority]. What happened in 2009 was that we didn’t have any flu production of vaccine in the U.S., and so we outsourced to Australia, and Australia said, thank you very much, we’re going to give it to Australians first. So, the U.S. was caught with its pants down, basically.

When we didn’t have the flu vaccine to give to people, the preparedness people were really upset. The HHS secretary was called in, the Emergency Preparedness secretary was called in.

And BARDA, which had been created around the same time, was tasked with responding to this problem, because the government was not going to have another situation where we didn’t have the flu vaccine when we had [the potential for] a flu epidemic.

So, BARDA built the plants; the biggest call for funding for flu went into building plants [that could manufacture flu vaccine].

There’s one in Texas, it’s basically a manufacturing plant to produce flu vaccine in tobacco plants. It’s huge, acres and acres of tobacco plants, but it’s never been used. They did one production run to show that they could do it, but I don’t think it’s ever been used. It’s a Texas boondoggle for sure.

There’s another one, I think Novartis got one, somewhere in the South, in Georgia. So, there’s a huge investment in these plants, the U.S. government built them, the big companies got them, dedicated to flu vaccine production, and that’s where the money went.

I was at a meeting in Mexico two weeks ago, and the head of BARDA, Robin Robinson, attended, and he said: We’ve solved two of the three problems. We solved production, in the U.S. We solved speed, so we can get vaccines to market.

The third problem was efficacy. [Robinson said that] we have problems with flu vaccine efficacy. We have not paid enough attention to efficacy.

And I said, “Well, we can help with that.”

So, we have a meeting planned.

ConvergenceRI: That’s great! You must be smiling.
DE GROOT:
Yes, I’m smiling. It’s been a long road. I think we have been getting serious traction. It also looks like we’re in line to get a government contract, working with folks at Harvard, working with the Department of Defense, on a vaccine for a bioterrorism agent. It’s not a lot of money, but it’s exciting.

The most exciting development [for us] is that when a virus attempts to camouflage itself, making itself look like the human immune system, trying to hide, we can now basically change the sequence so that now it can be seen again, and make it look like the flu [again], using the same computer [immuno-informatic] programs.

Now that we’ve shown that, by doing that, you can get a better response, you can go in and tinker with the viruses.

That’s the next step, to make vaccines better. That’s what BARDA wants to know about.

And we have proof.

ConvergenceRI: Here in Rhode Island, there seems to be so much new activity percolating up within the biotech industry community, such as the plans for Cambridge Biolabs to build a new facility in Providence. How does EpiVax’s work on vaccines fit into that?
DE GROOT:
Vaccines are not sexy to a lot of people. But I think where we’re going with vaccines, we are getting to the idea we’ve been striving for, which is: personalized vaccines.

I think, if we get the immuno-informatics tools to the point when we can run a sequence and we can build you a vaccine, we can have standardized vehicles to deliver to you a vaccine, made just for you.

I’m a vaccinologist. When I hear people blaming vaccines for a million things, I get upset. You have to look at the big picture.

On the other hand, can we make vaccines better? Absolutely!

We still use technology that’s so antiquated. When you think about Pasteur, he was shaking and baking, that’s what we call it.

Shake up a flask of bacteria, bake it and inject it. That was the vaccine technology, and it hasn’t changed [that much].

All we do is do is have [companies with] huge buildings where they grow bacteria, and kill it, and that’s your vaccine.

Can we simplify that? Can we give you just the things that turn on your immune response, and not any of the other stuff? Yes we can.

ConvergenceRI: How do we get to the personalized vaccines?
DE GROOT:
In Rhode Island, all the developments you mentioned, such as Cambridge Biolabs, are all great. I think it’s great that they’re going to build out more space for people to move into.

We could spin off a company, but probably not. We considered spinning out Tregitope. But it didn’t make sense. Why would we give up ownership of something we that we think is so valuable?

[The Congressional delegation], Senator Whitehouse and Senator Reed, they get it. So do Cicilline and Langevin.

We don’t have a lobbyist, we have our Senators, and we have great access. That’s one thing that Rhode Island wins, hands down, is our access. They are so responsive and engaged, we have no issue with their engagement, at least not with us, they totally get it.

[The problem is] the state’s legislature. Look at 38 Studios, not to go back to that haunting story, and how they invested that money. If they had invested that money in this company, we would be way farther along than we are, we would have terrific trials, we would have a drug…

I contacted them. I heard about [the $75 million for] 38 Studios.

OK, so you just wasted a huge bunch of money, supposedly, there’s a bunch left in the bank, how about giving us some of it to develop our drug for auto-immune disease, a really important platform.

The response? We’ll let you know when the next round comes around, and you can apply then.

You know, it was all about connections. So much money was wasted, a wasted opportunity that ruined the state. When you could have put the money in companies that had proven track records, with peer-reviewed, important science.

I’m still angry. I’ll never forgive that. 

ConvergenceRI: How has the implementation of health care reform changed the demand for services at the Clinica Esperanza? Have you seen a continued demand for services?
DE GROOT:
It’s an interesting transition. In fact, a lot of patients have been able to access Obamacare.

The biggest gap is with the immigrants that have been here for a certain period of time, that have applied for regular status, and they have tax ID numbers, and they are paying taxes, but they don’t have access to health care the way that everybody else does.

They have access if they can pay for it, which, of course, they can’t afford.

They are working, they are paying taxes, but they can’t vote. And, they don’t have access to Obamacare the same way that everybody else does.

To me, that’s wrong. This is a country of immigrants. They are some of the hardest working people. Who are the people with the highest number of people in college? First generation immigrants.

In terms of demand, there has been little change in the numbers. Before Obamacare, there were an estimated 140,000 with health insurance. We don’t know the number today, but they’re saying that about 40,000 people don’t have insurance now.

So, if we take care of 2,000, and the R.I. Free Clinic takes care of 2,000, that’s 36,000 people in Rhode Island who still don’t have health care.

It’s important, because these are people who do cost the system money. If they get sick, they go to the emergency room. It’s got to be more expensive to take care of them that way.

There should really be an investment in healthier lifestyles in the state.

ConvergenceRI: What is the greatest challenge you see for the biotech sector to grow in Rhode Island?
DE GROOT:
One of the biggest crises we face as a company is the skills gap. This year, we hired five new people, almost all of them came from out of state. They were working in Massachusetts, but they lived in Rhode Island, and we finally convinced them to come back home.

We really have a problem getting people who have the skills – and all those people we have to train, by the way.

So, I think we have a real problem, we have a deficit of people who can work at the entry level [for biotech] in this state. We need to keep people here after they graduate.

We rely a lot on people from the biotech program at URI – they actually have skills, they know how to keep a notebook.

ConvergenceRI: Do you think that EpiVax will become involved with work on Ebola?
DE GROOT:
Ebola is huge, it’s a real problem. I think that we should be paying more attention to it. It’s already spread to three different countries. It’s completely disrupting the health care system. People are panicked.

It’s pretty dramatic. You bleed from your nose, ears, eyes and mouth. People will notice if you have it.

We need to address this. We have the technology; we can address it. Let me at it; I’d be happy to work on that.

But I can’t go down to D.C. and say, “I want to work on Ebola, boys.”

I’ve let the people know at BARDA. We could work on this, if they want us to. But they’re going to go to Burberry’s – they’re going to big companies and purchase the thing that they think is the right approach. That’s not going to work.

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