Could the Flu Become History? An Israeli Vaccine May Make It a Reality

The results of final clinical trials are due soon, capping two decades of work by Weizmann Institute Prof. Ruth Arnon and the startup BiondVax

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Professor Ruth Arnon, 2020.
Professor Ruth Arnon, 2020.Credit: Tomer Appelbaum
Anat Georgi
Sagi Cohen
Anat Georgi
Sagi Cohen

A year and a half ago, biochemist Prof. Ruth Arnon, Israel Prize recipient for medicine and past president of the Israel Academy of Sciences and Humanities, received an email from the editor of a science journal. The editor asked whether she planned to attend a conference on multiple sclerosis that was to take place a few days later. Arnon, who was one of the scientists responsible for the research that led to the MS treatment, Copaxone, said she wouldn’t be attending, but was sending a researcher from her lab at the Weizmann Institute of Science.

Little did Arnon imagine that the editor’s interest was driven by a deeply personal and moving story. It turned out she had been suffering from MS, had started to lose her vision and had to leave her job. Her doctor decided to substitute the MS drug she had been taking with Copaxone. The woman’s eyesight was saved and she was able to return to work. “She wanted to thank me for developing Copaxone,” recalls Arnon. “Stories like these could add years to my life.”

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Arnon is 86, and like many people her age she is spending these days at home. “My husband and I are both in a high-risk group, and I’m not taking chances. I go out into the garden to get some air, but I don’t go anywhere. We get what we need delivered, so everything is okay,” she says.

Nevertheless, she continues to work, talking by telephone with the researchers at the lab she heads at the Weizmann Institute and with colleagues via Zoom meetings. She has good reason to keep busy: Within less than a month the fate of a project that she has been working on for some two decades will be decided. It is meant to provide a comprehensive, long-lasting solution to one of the world’s most widespread diseases: Influenza.

The Weizmann Institute of Science, 2018.
The Weizmann Institute of Science, 2018.Credit: Ilan Assayag

The project involves developing a vaccine that would protect people from all strains of the flu with a single injection. A startup company called BiondVax Pharmaceuticals, led by founder Dr. Ron Babecoff, has been working on the universal flu vaccine for the past 15 years based on a patented technology developed by Arnon and Dr. Tamar Ben-Yedidia. Ben-Yedidia was a colleague of Arnon’s at the Weizmann Institute and is now chief scientific officer at the company.

The vaccine is now undergoing Phase III, or final, clinical trials involving large numbers of human patients. If later in the year it is shown to work and is approved by regulators, it could replace the seasonal flu shot given every year. That vaccine changes from year to year, based on what the World Health Organization expects will be the most common flu strains in the coming year.

At a time when the entire world is looking for a coronavirus vaccine, there’s a chance that a universal flu vaccine will get approval?

“If everything goes according to our plans, then yes, it will be approved before they find a coronavirus vaccine. You have to remember that this coronavirus is a new one for humans. While we are familiar with the coronavirus family, we are still learning about the type that has attacked the world in the last few months. Most of the coronaviruses have mild symptoms, such as a cold and a fever, but in the recent past there were two epidemics, SARS and MERS, that came from more violent strains of coronaviruses. In both cases, they disappeared at the end of the season and didn’t return.”

Is there any significance to the fact that the coronavirus has flu-like symptoms? Is it a similar disease?

“The coronavirus is completely different from the flu even if the symptoms are similar. The anti-flu vaccine we’ve developed won’t work against the coronavirus.”

"There's no wonder drug that will provide an answer to the current outbreak."

Are the forecasts that a coronavirus vaccine will be developed within 18 months reasonable?

A pharmacy housed in a former movie theatre. April 2020.
A pharmacy housed in a former movie theatre. April 2020.Credit: BRIAN SNYDER/REUTERS

“Developing a coronavirus vaccine demands time, even if they decide to shorten the process under pressure from the public. It’s not something you can do in two months. You have to examine the efficacy and safety of every vaccine and that alone takes many months. If you want to manufacture it in commercial quantities, researchers will have to wait months longer for the results of clinical trials. There’s no wonder drug that will provide an answer to the current outbreak. Maybe we’ll be able to develop a vaccine or drug by next winter. There are a lot of scientists and biotech company teams who have dedicated a lot of resources in this direction. I hope one of them will succeed.”

Why has it taken so long for your team to develop its flu vaccine?

“In the case of the flu, we pursued something entirely different from the vaccine required for the coronavirus. The flu virus is seasonal – it arrives in the winter, disappears at the end of the spring and returns the following winter. The flu’s special characteristic is that it changes every year and so the vaccine is also seasonal. A vaccine produced one year won’t be effective the next year. So, every year you have to make an educated guess in advance what strain of flu will be coming and on that basis to formulate the vaccine.”

How do you make that guess?

“The WHO monitors the flu virus that appears in different parts of the world, usually in East Asia, where the flu generally arrives six months before it reaches the northern hemisphere. They examine which strains are the most widespread, generally around April every year, choose three or four of them and then ask vaccine makers to provide a solution. The process of preparing a vaccine is long and complicated, so they need to begin working immediately so the vaccines can be on the market by October, ahead of the winter.

“The system for predicting isn’t always entirely successful. As a rule, it provides a solution for half of flu sufferers. Two years ago, for example, the forecast wasn’t right, so the efficacy of the vaccine was low, around 20%. For at-risk populations, the efficacy was even lower.”

A plant of Israeli pharmaceutical giant Teva in Kfar Saba, Israel.
A plant of Israeli pharmaceutical giant Teva in Kfar Saba, Israel.Credit: Ofer Vaknin

So what did your team do?

“In our research, we examined the virus’ proteins and began to work on a synthetic material containing proteins common to all strains of flu viruses and not subject to change, at least as far as we know at the moment. We found four of these. With the compound we created we vaccinated mice, then humanized mice [genetically engineered to have a human immune system] and found that they were protected from the flu. If we can give people such a vaccine, there will be no need to develop a seasonal vaccine every year. Even if there are some changes over time, our synthetic vaccine can be changed relatively easily.”

Arnon was born in Tel Aviv, the youngest of three children. Today she is the mother of two, grandmother of six and great grandmother of one. From a very young age, Arnon was attracted to math and physics. “I was bored in first grade, so they skipped me to second grade and I was bored there, too,” she told an interviewer years ago.

She got her bachelor’s and master’s degrees in chemistry and biochemistry from The Hebrew University of Jerusalem and her doctorate from the Weizmann Institute in 1960. After doing post-doctoral research at Rockefeller University in New York, she returned to the Weizmann Institute and in 1966 was named a full professor. Over the years she has served as the institute’s vice president and on the WHO’s steering committee.

She discovered Copaxone, together with Prof. Michael Sela, by accident, Arnon says. “We were interested in MS and we wanted to study the mechanism of the disease. To do this, we planned to induce a similar disease in laboratory animals. But to our surprise in the experiment on the mice, we not only created the disease but we suppressed it. As a result, we changed direction and the research eventually resulted in Copaxone.”

When Arnon realized that the compound she and her team had developed for the flu worked, she patented it so that she could continue working on it without fear of anyone copying the idea and in order to commercialize it. BiondVax was founded in 2005 to bring the product to the market. One of its backers is Marius Nacht, a co-founder of the cybersecurity giant Check Point Software Technologies. Last year, Nacht became BiondVax’s controlling shareholder with a 42% holdings through his aMoon venture capital fund.

Copaxone, developed by Prof. Ruth Arnon to fight multiple sclerosis.
Copaxone, developed by Prof. Ruth Arnon to fight multiple sclerosis.Credit: Copaxone

BiondVax was traded on the Nasdaq and the Tel Aviv Stock Exchange, but it dropped its TASE listing in 2017. It trades at a market capitalization of about $155 million after its share price jumped 2.5 fold over the last six weeks as the coronavirus pandemic spread.

The company is erecting a factory in Jerusalem to manufacture the flu vaccine in anticipation of final clinal-trial results by the end of the year. If the vaccine gets regulatory approval it could revolutionize medicine. If the trial fails, all the years of development and the money spent on it could go down the drain. Other efforts to develop a universal flu vaccine are undeway around the world, including at Mount Sinai Hospital in New York.

Arnon isn’t playing an active role in the company except as chairwoman of its scientific advisory committee. “I have stocks from when the company was founded and also shares I bought with my own funds to help the company at the start. Also, I believe in it and am waiting impatiently for the results,” she says.

BiondVax has enhanced the vaccine, by adding additional shared proteins to it, so that it will be effective against more strains of the flu virus.

“They put together a synthetic protein that contains nine proteins and demonstrated its efficacy in a vaccine given to mice that possess human tissue components,” says Arnon. “Then they conducted several trials with several hundred participants, and last year they moved to the final Phase III trial. In that trial, a total of 12,000 adults, including many elderly, participated. Last year, 4,000 people were vaccinated in the trial. This winter, 8,000 more people were vaccinated. Half of them were given a placebo and half were given the vaccine we developed. The trial had to be conducted over two years and in seven different countries to see its effect on a variety of different influenza strains.”

At the end of May, the results will be collected and analyzed for differences between the two groups. If the results are positive, that is the vaccinated group developed an immunity against the virus, regulators should then give clearance to market the vaccine – first in Europe and later the United States.

A patient receives a flu vaccine in Mesquite, Texas, January 23, 2020.
A patient receives a flu vaccine in Mesquite, Texas, January 23, 2020.Credit: LM Otero / AP

If the vaccine gets approval, does that mean that it will protect us from the next flu epidemic?

“Yes. If it is effective. Remember that we still haven’t got significant clinical results. Everyone today is preoccupied with the coronavirus and the growing number of fatalities, but every year hundreds of thousands of people around the world die from the flu – sometimes as many as 650,000 worldwide. No one relates to these numbers because we’ve gotten used to them. A universal vaccine like the one we’ve developed will prevent many diseases, including bird and swine flu, which can re-emerge without any warning.”

Naturally, the demand for such a vaccine will be huge.

“Commercial considerations were not what led us to the research. I would be very happy if it’s a commercial success and earns profits for BiondVax and for me. But the money is at the bottom of my considerations. It was never the thing that motivated me.”

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