PROVIDENCE – With some predictability, the flu season has arrived, just in time for Thanksgiving, early Christmas shopping, and a wave of bitter Arctic cold to magnify the symptoms of coughing, sneezing and wheezing.

The flu is an equal opportunity virus; it doesn’t discriminate by race, creed, religion, gender, income, sexual identity, health insurance or political ideology.

Months before each flu season, the Centers for Disease Control and Prevention, working with scientists around the world, oversees the production of a flu vaccine to offer what it hopes will be the best protection against the ever-changing, quickly mutating strains of the flu virus.

From a public health perspective, the yearly flu vaccine is a critically important prophylactic. As Dr. Michael Fine, director of the R.I. Department of Health said: “The flu is a serious illness that can keep you out of school or work for at least a week, and it spreads very easily.” By being vaccinated, Fine continued, “you are protecting yourself and the people you love by making sure that you won’t pass the flu to them.” [Putting his words into action, Fine, joined by R.I. First Lady Stephanie Chafee, an RN, held two no-cost flu clinics on Nov. 23 and Nov. 25 in Providence.]

And, every year, also with some predictability, new strains of the influenza virus emerge, often in China, and with it, fears of a pandemic, with potential devastation far beyond anything imagined by Stephen King. This year, the new strain that emerged was H7N9.

Science without fear
What has changed in the flu equation is that scientists have been able to develop a better understanding of the flu virus’ molecular structure and its epitopes – that portion on the surface of the antigen that is recognized by the immune system – to which an antibody can bind.

In April, Dr. Anne S. De Groot and her team at EpiVax (along with key collaborators), concerned by reports of the emerging H7N9 virus, undertook an analysis of the virus, using immuno-informatics tools. They discovered that H7N9 was a “stealth virus” – it contained far fewer epitopes that other flu strains.

Their “stealth virus” discovery was confirmed recently in clinical trials conducted by Novartis, a Big Pharma firm. Novartis reported on Nov. 14 that interim results from a Phase I clinical trial showed that only 6 percent of subjects achieved a protective response using a flu vaccine designed to promote an immune response.

[Novartis is promoting a vaccine that is adjuvenated – with an added pharmacological agent to increase the effectiveness of the vaccine. The trial compared the adjuvenated vaccine with the non-adjuvenated vaccine.]

De Groot told ConvergenceRI she was elated by the validation of her team's work. The Novartis clinical study, she explained, showed H7N9 flu was practically invisible to the immune system, compared to the standard flu.

“Only 6 percent of participants seroconverted,” De Groot wrote in an e-mail to ConvergenceRI. “The usual rate of seroconversion is higher than 80 percent for Influenza A strains!”

“Wowza. We love to be right.”

Webinar offered on new tools
More than just being right, De Groot is pushing hard to have national and world entities use EpiVax’s range of immuno-informatic tools to make better decisions – and better vaccines – to address flu pandemics.

Toward that end, De Groot is offering a webinar on Friday, Dec. 6, at 1 p.m., on her firm’s H7N9 vaccine design project, walking participants through the process of evaluating influenza strains step-by-step.

“You may have heard about the use of immuno-informatics tools for the design of vaccines before,” De Groot wrote, describing the webinar. “Are you curious how they could help with the analysis of new flu strains? Does the variation in vaccine efficacy relate to T cell epitope content, and could these same tools also be useful for evaluating vaccine efficacy post-facto? How are immuno-informatics tools helping design, evaluate, and improve vaccines?”

The webinar, she continued, will answer many of those questions, as well as explain how EpiVax uses its iVAX vaccine design tool preparedness.

H7N9 prognosis
The new, avian-origin flu H7N9 virus first emerged near Shanghai in February. During the spring, there were a reported 135 human infections, and 44 deaths, according to the CDC.

Four new cases were reported in October, which coincided with the arrival of cooler weather and were not unexpected, according to the CDC.

The fact that most patients with H7N9 flu have had severe respiratory illness, with about one-third leading to death – as well as the pandemic potential of this virus, has the CDC and scientists around the world very concerned.

“What China has done to control the potential spread is to pretty much close all the live poultry markets,” De Groot told ConvergenceRI in a recent interview. “The biggest problem is that birds don’t get sick with it, humans do.”

Given the poor antibody responses to H7N9 flu strain, De Groot continued, it’s difficult to use the traditional surveillance technique of testing antibodies to see if someone has been infected. “It’s a really bizarre virus,” she said. The thinking, she continued, “is that the virus may be circulating but not being detected.”

De Groot said that EpiVax is working with partners in Japan and in China to develop new vaccines based on her company’s analysis of the H7N9 epitope structure.