Innovation Ecosystem

Responding to the threat of an influenza pandemic

EpiVax has developed a tweaked vaccine to combat H7N9 flu that is in clinical tests in Australia, but are the major U.S. public health authorities paying enough attention?

By Dr. Annie De Groot
Posted 3/13/17
The growing threat of a potential pandemic as the result of the H7N9 avian flu virus has alarmed public health authorities around the world, in large part because of the ineffectiveness of current flu vaccines to combat what EpiVax, a leading Rhode Island biotech company, has diagnosed as the “stealth” qualities of the virus.
In turn, EpiVax has developed a new vaccine, using its immuno-informatics technology, which is now in clinical trials in Australia. The question is: will the leading U.S. health authorities commit to spending billions on an ineffective vaccine? Or will they invest in the work of EpiVax?
With the current Trump administration plans to cut back on public health infrastructure funds, how will it affect the capability to respond to a global flu pandemic? Which scientists from Rhode Island will be joining the March for Science on April 22 in Washington, D.C.? What role can the Rhode Island congressional delegation play in helping to support the vaccine work being conducted by EpiVax?
The all-day IDeA symposium on March 14, to be held at the Warren Alpert School of Medicine at Brown, will showcase the ongoing cutting-edge research being done in Rhode Island by a host of collaborative research enterprises. The event speaks to the strength of the current biomedical innovation ecosystem in Rhode Island.
What perhaps is missing from the discussion, something that may be ingrained in the work that scientists do, is the relationship of failure as a necessary part of the innovation process. The desire to translate the ongoing research into an economic development platform often leads to unrealistic expectations about the long-term nature of innovation.

PROVIDENCE – Albert Einstein once said that the definition of insanity was to do the same thing over and over again and expect different results. Repetitive thinking seems to be prevalent in the influenza vaccine industry.

A case in point: There’s a new H7N9 avian flu virus out there. Due to its high rate of lethality [20-40 percent] and pandemic potential, H7N9 preparedness has becoming a priority for public health officials.

The World Health Organization [WHO] is discussing changing the “seed strain” and BARDA [the U.S. Biomedical Advanced Research and Development Authority] is contemplating issuing a new contract for production of the vaccine, according to recent reporting by STAT.

The U.S. Centers for Disease Control and Prevention has placed avian influenza H7N9 at the top of the risk scale for its potential for significant pandemic impact.

But the last H7N9 vaccines to be developed were an abject failure. You heard that right.

Novavax’s $97 million vaccine induced only 6 percent seroconversion [as compared to 89 percent for H1N9]. Why? Due to the ability of the virus to be ‘stealth.’

We ask: why would a ‘new’ vaccine, based on the emerging strain, be an improvement over the old, ineffective one? There is reason to be worried.

The number of human cases of H7N9 has rocketed – more than 450 have been reported since last fall.

Add this news: a new strain of H7N9 has emerged in Tennessee [with the same outside, but different internal genes]. You can see why U.S. health officials are concerned.

Making a better vaccine
The failure of H7N9 vaccines was predicted. In April of 2013, within days of the publication of the H7N9 sequence, researchers at EpiVax reported that H7N9 virus was a “stealth” virus, because there were too few T helper epitopes in H7NA to drive effective antibody response.

The scientists compared the new virus with H1N1 and H3N1 and made the prediction before any vaccines were available. The original finding was published in August of 2013.

As predicted, vaccines against the new strain were poorly effective: In stark contrast with vaccines for seasonal influenza [H1N1], H7N9 vaccines generated very low immune responses without adding strong adjuvants.

Seroconversion rates of only 6 percent and 15.6 percent were reported in Phase I clinical trials [as compared to 89 percent for similar unadjuvanted seasonal H1N1 subunit vaccines]. The EpiVax prediction was right on target.

Immune camouflage
H7N9 is truly “stealth.” One of the ways by which the immune system detects infection is by presenting short peptides derived from the pathogen to T cells, which distinguish between foreign and self-antigens.

Researchers at EpiVax and the University of Rhode Island also produced evidence that the H7N9 hemagglutinin (HA) surface protein had evolved a set of mutations that make it similar to human proteins, and the presented peptides thus resemble self-antigens, activating and expanding regulatory T cells.

These new sequences actively suppressed immune responses – a new means of pathogen escape called camouflage.

Testing the hypothesis
EpiVax tested the immune camouflage hypothesis by challenging peripheral blood mononuclear cells from naïve donors with H7N9-derived peptides. Remarkably, the more the peptide resembled a self-antigen, the less it was able to elicit a T-cell response.

To prove the point, EpiVax “immune engineered” a better vaccine by changing the sequence of the H7 HA Treg epitopes.

In studies carried out at three independent laboratories (publications in preparation), the vaccine proved to be more effective than the “wild type” vaccine. This “optimized” H7 HA vaccine was produced by Protein Sciences corporation. It is currently in clinical trials in Australia. [Thanks to Nik Petrovsky.]

What is the message?
Before WHO, BARDA and the National Institutes of Health make the decision to order up an entirely new vaccine to protect against the new H7N9 viruses, they should consider whether the new strain is still a “stealth” virus [that it contains the Treg epitopes discovered in the original strain].

And, in the interest of science, EpiVax scientists would be happy to share their “immune-engineered” fix. If not, BARDA and the CDC will certainly make the same mistake they made in 2013.

What was that definition of insanity? Anyone?

Dr. Anne De Groot is the CEO and CSO of EpiVax. This story was adapted from her most recent blog post.


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