The avian flu virus – BiondVax was on track to begin human clinical trials of the new vaccine, which has already proven effective on animals.Israeli company BiondVax doesn’t claim to have the answer that will allay the mounting fears of a worldwide pandemic of avian flu.
But they hope that in coming months, their long-term project to develop a ‘universal flu vaccine’ may help make a contribution towards finding an effective way to avert this global health crisis. An outbreak of the avian flu virus in the US could infect one-third of the population, according to a US government report released last week.
The vaccine is based on nearly two decade of research by world-renowned scientist Prof. Ruth Arnon of the Weizmann Institute. BiondVax was on track to begin human clinical trials of the new vaccine, which has already proven effective on animals, but the current flu crisis is speeding things up.
The company’s carefully crafted business plan was to try to bring the ‘universal flu vaccine’ to market in 3-5 years, according to one of BiondVax’s founder Isaac Devash. But now there is a “new urgency” in the company’s development of its product which has led us to adjust our plans, he told ISRAEL21c
“Obviously, when this threat emerged, we knew we had to test our vaccine on it,” said Devash, who served as chairman of the company in its formation phase.
“We are now checking the recognition of the antibodies that an animal creates after vaccinations against the specific of the H5N1 (avian flu),” reported company president and CEO Dr. Ron Babecoff. “We are vaccinating animals with the vaccine – we’re taking the blood and putting it together with proteins from H5N1 and seeing if there is recognition. We will have the lab results in a month.”
He added: “In parallel, we want to do a challenge trial with animals and the avian flu – take a group of animals vaccinated with the vaccine, one with a placebo, expose them to the live virus – because working with the live virus is very dangerous… we can’t do it in our current laboratories. The Israeli Veterinary Institute has agreed in principle to start this experiment with us. We estimate that it will take six months to complete these experiments, but by then we will have quite strong evidence to show that it has protective ability against the virus.”
Babecoff is optimistic about the universal vaccine’s effectiveness on avian flu because it has successfully protected mice – which are equipped with immune systems that mimic those of human beings – against a number of flu strains. All of the vaccinated mice survived and the non-vaccinated animals died.
“We believe it will be effective,” Babecoff said.
If it does indeed prove effective – and if the avian flu remains a threat – then BiondVax’s business plan may unfold very differently than originally planned.
The company’s approach to fighting flu differs from the way the battle against the flu is traditionally waged. Traditional flu vaccines are the result of a longstanding process: world health bodies work every year to identify the most common strains of flu circling the globe, using 120 monitoring stations worldwide to identify new strains. Using this information, they predict which virus strain will be prevalent in the forthcoming season. These strains mutate slightly every year, and change radically approximately every 30 years.
A selection of 3 existing flu strains is made every year by the World Health Organization experts that presumably will be similar to the strain expected that year. These seed strains are sent to drug companies which develop a vaccine to fight it. These vaccines – developed according to the classic method originated by Louis Pasteur – are isolated, inactivated versions of the virus one is trying to fight. The virus development and production process is long, and there is a danger that while one vaccine is being developed a new mutation may have already emerged.
Arnon’s breakthrough was a decision to look at the flu virus in a conceptual manner – looking for the ways in which all flu viruses are similar. The developer of Teva’s Copaxone drug for treating multiple sclerosis, Arnon, 71, is a world-famous scientist whose list of prizes and honorary degrees includes the French Legion of Honor, the Wolf Prize for Medicine and the Israel Prize for Medicine, and has published over 400 articles on immunology. She remains intimately involved in BiondVax’s work, overseeing the vaccine’s development on its research and development committee.
“Dr. Arnon decided not to chase a specific strain of virus. She said ‘let’s identify the common components of all flu viruses, use genetic engineering to duplicate those common parts of the virus, and create a vaccine which – no matter what virus will come – will vaccinate you,'” explained Devash, who then uses the following analogy.
“Think of your nose as the moon and the flu virus as an alien space shuttle that lands there trying to conquer it. Until now, developing a vaccine meant looking at the shape and the color of the specific space shuttle. But every space shuttle – every virus – is different and so you have to quickly adjust your fight depending on who lands. But she said, ‘OK, let’s look for functional components that let us know it is a space shuttle – never mind what kind. Every shuttle has to have stairs, for example, so the aliens can get off and invade you. So let’s look at a way to identify what the stairs are made of and figure out a way to deactivate them through a vaccine. If we do that, we have a tool against any alien spaceship — virus — not just one that is a particular size, shape, or color.'”
These functional elements – the so-called ‘stairs’ Devash refers to – “are known to science, but no one thought to use them as a source of a vaccine” previously, Devash said.
One of the virus proteins Arnon probed was a protein called Hemagglutinin found on the surface of the flu virus and found that it hid a peptide which appeared when the virus attached itself to a living cell. She discovered that this hidden part remains fixed in all the viruses, even when the external envelope undergoes significant changes, which prevent the body from identifying the virus. Over the following 10 years, Arnon and her colleague, Dr. Tammy Ben Yedidia succeeded in proving that this peptide could serve as a serum for a vaccine, which enables the immune system to recognize and to stop various flu strains.
Babecoff says that Arnon’s work is “a change in the paradigm. Scientists were sure that you can’t vaccinate with peptides. She proved that it’s not true.”
A vaccine that can overcome mutation is an extremely attractive prospect – one of the current fears, even as nations stockpile vaccines against the current strain of avian flu, is that it may mutate into a version that these vaccines do not address.
The BiondVax vaccine is different from what is currently available in other ways as well. In Arnon’s experiments on mice, the vaccine was long-lasting – the company believes it may be good for five years. The new vaccine activates both arms of the human immune system (B- & T-cells) resulting in over 95% protection.
It is also not injected – one drop of the vaccine inserted in the nose is effective.
Although Arnon has been pursuing this research for many years, it is only within the past five years that BiondVax was created to commercialize her research.
Devash and his fellow investors, while they couldn’t foresee the onset of avian flu specifically, knew that the need for a better approach to fighting the waves of flu outbreaks would become necessary.
“The writing was on the wall – it’s a question of time for a pandemic will hit humanity, and we need to be ready,” he said.
The results of Arnon’s research have so far excited and inspired the company’s backers.
“She’s had very dramatic results – 100 percent of the mice vaccinated have stayed alive – and despite changing the flu again and again and again. When Professor Arnon took the study one step further and tested it on mice into whom white blood cells had been injected, known as ‘humanized mice’ to see if it works, the results were equally impressive,” said Devash.
Babecoff, a veterinarian with 10 years of experience in the pharmaceutical industry co-founded BiondVax in 2003 after investigating new projects with business potential. Once he looked into Arnon’s research, he knew he found the right project.
Recently, the company completed a $4.5 million round of raising capital with which they are completing their new facilities, and they are expecting grants from the government, to help fund the human trials that are set to begin in the first quarter of 2007.
Babecoff noted that unlike regular Phase One trials of drugs, which normally only demonstrate safety, “Phase one trials of vaccines not only demonstrates the safety of the product as in other drugs – but gives an indication of how the immune system is reacting to the vaccine. We expect to see elevation of antibodies, proliferations of all kinds of T-cells, an activation of the cellular immunity and the antibody immunities. We plan for the Phase Two trials – scheduled for the fourth quarter of 2007, to enter the ‘challenge mode’ where you take volunteers, you vaccinate them with vaccine, and others with a placebo and you expose them to a mild type of influenza virus, and you compare the illness rate.”
If these trials are successful, he expects that the company would join with a major pharmaceutical manufacturer for the complex Phase Three stage and development of a vaccine to bring to market.
Again – all of this could change or be accelerated if the tests on the avian flu virus are extremely successful.
Devash says the company’s work is “on the radar” of some large companies as developing a possible answer to the avian flu. They are in close contact with the World Health Organization in Geneva, which has been monitoring all of the attempts at a vaccine worldwide. Arnon has been invited to address a WHO conference on avian flu in December, when the company hopes she will be able to present the initial results of tests of the vaccine against the killed Avian flu virus.
Devash says that they are optimistic about their ability to help avert the avian flu crisis, but still cautious.
“I would say that there are about ten different approaches being used to coming up with a vaccine – and about six or seven are based on the same method – the current existing method of vaccination. Ours is in the minority of trying to do something completely different.”