The race for Israel's homegrown COVID-19 vaccine

HEALTH AFFAIRS: The father of the BriLife initiative explains Israel’s strategic imperative to have its own vaccine.

 Health worker prepares a Covid-19 vaccine at a temporary Clalit health care center in Jerusalem, September 30, 2021. (photo credit: YONATAN SINDEL/FLASH90)
Health worker prepares a Covid-19 vaccine at a temporary Clalit health care center in Jerusalem, September 30, 2021.
(photo credit: YONATAN SINDEL/FLASH90)

Israel is on the verge of finalizing a COVID-19 vaccine whose creators believe could offer better protection against variants than its international counterparts such as Pfizer.

In an interview with The Jerusalem Post, the father of Israel’s BriLife coronavirus vaccine, Prof. Shmuel Shapira, predicted that when the country’s vaccine is ready, “it will be better” than what its citizens have today.

BriLife was developed by the Israel Institute for Biological Research (IIBR). Shapira served as its director for the last eight years, stepping down in May. He recently published a book in Hebrew on his experience last year called The Pandemic Circus about Israel’s race for its own antidote to the global pandemic.

On a cold Saturday night on February 1, 2020, Shapira was watching a movie with his wife when his phone started ringing and an “unknown caller” appeared on the screen. At first he ignored the buzz, but after four or five attempts, he answered.

“I was asked to come to a meeting on Sunday at noon with Prime Minister Benjamin Netanyahu to discuss the possibility of manufacturing vaccines at IIBR,” Shapira recalled.

“The request was rational,” he said. “We were the only institute capable of planning and manufacturing vaccines. We were already doing it.”

 DEFENSE MINISTER Benny Gantz, left, speaks with then-director of the Institute of Biological Research, Prof. Shmuel Shapira, at the center’s laboratory in Ness Ziona, last year. (credit: ARIEL HERMONI/DEFENSE MINISTRY)
DEFENSE MINISTER Benny Gantz, left, speaks with then-director of the Institute of Biological Research, Prof. Shmuel Shapira, at the center’s laboratory in Ness Ziona, last year. (credit: ARIEL HERMONI/DEFENSE MINISTRY)

What exactly IIBR was working on is information that Shapira is not quick to share. The institute operates under the auspices of the Prime Minister’s Office and works closely with the Defense Ministry. Its strategic and technical capabilities are shrouded in secrecy.

“We manufactured the smallpox vaccination for the entire population of Israel,” Shapira said. “There were other vaccines as well, but I cannot say what they were.”

“We opted for an approach that is, on the one hand, modern and, on the other, more conservative and less bold than the other vaccine makers chose,” Shapira said, explaining that BriLife is based on a technology that has been in existence for three or four years and has already proven to be successful against the deadly Ebola virus.

BriLife is a vector-based vaccine. The vaccine takes the vesicular stomatitis virus (VSV) and genetically engineers it so that it will express the spike protein of the novel coronavirus on its envelope.

Once injected, it does not cause disease by itself. Instead, the body recognizes the spike protein that is expressed on the envelope and begins to develop an immunological response. Moreover, unlike other vaccines, this one binds to the exact cell in the lung that is targeted by the novel coronavirus.

The last volunteer in Israel’s Phase II clinical trial was inoculated earlier this month. The first volunteer in a Phase IIb trial in Georgia is expected to get jabbed at the start of November, NRx chairman Prof. Jonathan Javitt said. The Phase III trial should start by February.

IIBR gave NRx exclusive worldwide development, manufacturing and marketing rights for BriLife in July after more than three months of negotiations and a year of bureaucratic delays.

Javitt said that the Phase III trial will involve 20,000 people and last about six months, but “if the vaccine performs the way we hope it will against some of the new variants, I can imagine some countries thinking about giving it emergency use authorization in a third of that time.”

NRx brought in outside experts to evaluate BriLife before signing, and Javitt said “the feeling was unanimous that there is innovation associated with the IIBR vaccine that potentially addresses this terrible virus better than other technologies.”

Early clinical experiments hold up that the vaccine could be more effective against mutation and confer lasting immunity, said Prof. Yossi Caraco, director of Hadassah’s clinical research unit, who served as the national principal investigator for the trial. He said the rate of side effects is much lower and they are less severe than with Pfizer and Moderna, and the level of neutralizing antibodies the shots produce is “promising” and even “encouraging.”

Prof. Cyrille Cohen,  the head of the immunology lab at Bar-Ilan University, who is not connected to IIBR or the vaccine, said that while it is too early to tell the vaccine’s efficacy, he does believe it has a chance for success and would be a good candidate for booster shots at some point.

“How will it perform against other vaccines already on the market?” Cohen asked. “The competition is tough.”

IIBR WAS founded in 1952 as a merger of the Hagana’s Hemed Bet biological warfare unit and another research division of the Defense Ministry that had been established after the War of Independence.

Convicted Soviet spy Avraham Marcus Klingberg was among IIBR’s founders and later served as deputy director of the institute.

From its outset, the institute that sits in “Israel’s green city,” Ness Ziona, has had a dual identity. On the one hand, it conducts highly classified scientific research known to be relevant to the country’s national interests. On the other, it serves as a public research institute that contributed to the development of a vaccine for polio and brand name drugs sold in Israel and abroad.

The institute prides itself on its defense-related research. But in terms of its alleged offensive capabilities, little remains known except that Israel has not signed the 1972 Biological and Toxin Weapons Convention and that, according to foreign reports, the Mossad has attempted to use biological weapons at least twice to assassinate people.

In October 1998, it was discovered that an El Al cargo plane that crashed six years prior in Amsterdam was carrying a shipment of DMMP, a chemical used in the manufacturing of sarin nerve gas, which was meant to be delivered to IIBR, according to a New York Times report.

“I don’t want to talk about the reason we are secret or what they say, with all the legends and everything,” Shapira said. “Our only mission is to defend.”

Shapira was at IIBR for eight years. He came to the institute after serving as the head of the Hebrew University’s School of Public Health and deputy director of Hadassah-University Medical Center. He has published several books and hundreds of scientific papers.

A year after arriving at IIBR, he said, he defined the institute’s main mission as preparing for a pandemic, but without support for this mission “we did it under the radar.” They focused on upgrading their diagnosis capabilities and on developing a flexible vaccine candidate.

When Netanyahu asked IIBR to develop the vaccine, the institute was therefore ready, and said it could make 10 million to 15 million vaccine units, enough to inoculate all eligible citizens and the Palestinians.

On August 6, 2020, Shapira appeared on Zoom with the prime minister and told him and the public, “Six months ago, you dispatched us to bring a vaccine and antibodies to the State of Israel. We have carried out the mission, and are carrying it out in the best way possible. We have an excellent vaccine. This is the first vial of the vaccine; since last Thursday, we have a vaccine.”

A week later, when Shapira presented the vaccine to the Knesset, MK Einav Kabla said, “We are all waiting with expectation for the big news about a vaccine that will begin to put an end to the complicated situation we are in, which has implications on every area of our lives.”

IIBR’s success “is the hope of the entire nation of Israel,” she said.

But three months later, Shapira was back at the Knesset complaining that “had we not encountered overregulation, we would have progressed more.”

Meanwhile, Israel signed a deal with Pfizer, and by December 2020 the country’s valiant vaccination campaign began.

To date, more than 6.1 million Israelis have received at least one shot, and more than 3 million three shots.

WHY NOT just give up on developing an Israeli vaccine?

“The pandemic is not over, and there will be another pandemic,” Shapira insisted. “You will see it in your lifetime.”

And he said that Israel having its own vaccine is a strategic initiative.

“Maybe tomorrow we will not have such a good relationship with a certain company” and Israel will not be given the tens of millions of vaccines it needs so fast, he said. “You cannot trust it. Just like we need to be able to bake bread and manufacture artillery, there are certain basic needs that cannot be left for others, especially when dealing with matters of life or death.

“Israel is a country with good scientists and a strong biotech industry. We should be capable of manufacturing vaccines whether Pfizer exists or doesn’t.”

Moreover, he said that in his estimation, Pfizer is not as good as it first appeared.

“I think the vaccine that Israeli citizens are vaccinated with is not an A vaccine,” Shapira said. “I don’t know which grade to give it, but a vaccine that only functions for a few months is far from being perfect.”

He is not anti-vaccination, and he has gotten jabbed three times, but he said he does have some concerns about potential long-term side effects of the vaccine.

“The main advantage of mRNA vaccines is that they can be designed very quickly. The disadvantage is that their technology is unknown, raising all kinds of safety issue questions – certainly for long-term side effects,” Shapira said.

Though he did not want to be specific, he said in a conversation with Yediot Ahronot that he knows from “my close circle and conversations” he has had with doctors that there are “significant” side effects that could be associated with the vaccine.

“I don’t think that they were covered up on purpose, but I think digging deeper into the possibility of side effects was less convenient” when running a mass vaccination campaign, he told the Post. “I don’t think anyone tried hard enough to look for side effects.... A year is a very short experiment.”

The US Food and Drug Administration has given full approval to the Pfizer vaccine in August. In its statement of approval, it noted that “available data from short-term follow-up suggest that most individuals” recovered from any side effects they experienced. However, “information is not yet available about potential long-term health outcomes.”

He also said that the booster campaign was decided on “too hastily” and that he does not believe Israel was transparent in admitting to citizens that giving them a third shot was “experimental.”

Shapira said anyone under 65 who is getting the third shot should be informed that it was not approved by the FDA, told what the benefits and harms might be, and asked to sign a consent form.

“I am a man who is aware of what secrets are and respects secrets,” Shapira explained. “But there was a lack of transparency. Why were parts of the Pfizer contract hidden? Why were coronavirus cabinet meeting minutes hidden? I think there was too much business and too little science. In a battle between science and business, science should win.”

In his new book, he describes Israelis as “guinea pigs” who “paid a fortune to be part of an experiment,” though he said in the interview that this is not necessarily a bad thing.

“I don’t think anyone did Israel a big favor. We paid a big price for these vaccines – more than any other country. And the other thing we paid with is something more valuable, data,” he said. “I think it was the right decision to vaccinate the population with the available vaccine... but Israel became a lab for the first and second doses of the vaccine, and now we are doing it again with the third dose.

“Being a guinea pig is not necessarily bad. You can be smart mice,” he continued. “Whether it was a mistake or not, we’ll only know in the future.”

And he pointed out the paradox that Israel is among the most vaccinated countries in the world with one of the highest infection and mortality rates.

“If the vaccination is so good, why are so many people sick?” Shapira asked.

He said that when the government chose Pfizer and started to see its preliminary results, it abandoned the other health measures necessary to control the pandemic. It also left IIBR and its vaccine behind.

“I have documentation that proves government officials worked to delay our progress for months on end,” he said.

He told the Post that not only were the 80 scientists working on the vaccine not given the support they needed, but sometimes they faced nonscientific, bureaucratic obstacles by politicians and others. The regulatory bodies worked slowly. Meetings were infrequent and often delayed. Decision-making took too long.

The government invested only NIS 176 million in the project, compared to the $3 billion budgets of other companies working on a COVID vaccine.

“It was really David versus Goliath, and we did it,” Shapira said. “We had this really good product in our hands, and now the people of Israel cannot enjoy it.”

IN HIS book The Pandemic Circus, he also talks about the government’s mismanagement of the pandemic and calls for a government inquiry into its actions.

“I heard and saw it all and was often shocked or stunned into disbelief by what had transpired,” Shapira wrote.

But he said the goal is not to throw the country’s leaders under the bus, but to learn for the next time around.

His advice is multifaceted.

First, he said, Israel needs to establish a better communications program, like it had during the Gulf War, when one voice offered twice daily updates, explained what was happening and told the public what is best to do.

Data should be more accurate, as well, he charged. The Health Ministry numbers were often inconsistent and played a role, he believes, in the government’s zigzags.

Shapira said that Israel needs to better tap into its mayors.

And, of course, he said that the country needs to invest in building a vaccine manufacturing facility that could be ready for next time.

When Netanyahu instructed IIBR in February 2020 to develop a coronavirus vaccine, he also spoke of establishing a vaccine factory in Israel. In August, when IIBR announced it was ready to launch a Phase I clinical trial, the prime minister said that he had asked the institute to start setting up the production plant, parallel with the first human trials, so that Israel would be ready if the trials were successful. However, little or no progress was made on this manufacturing site.

Shapira said he took several visits to the city of Yeroham, whose mayor, Tal Ohana, told the Post in a previous discussion that there is a “detailed plan” for launching a manufacturing facility in her town.

She had said she hoped that this facility would manufacture BriLife.

“We really believe in the Israeli vaccine,” Ohana said. “It is the only way to be vaccine independent. I really hope that IIBR gets final confirmations from the Food and Drug Administration and can then begin manufacturing in Yeroham.”

Shapira said he is “skeptical” and “cynical” that such a factory will ever be established, even though “it is feasible” and “I think it should happen.”

He said that “now everyone is talking about vaccines. But when, God willing, this will all be over, then we will move on to other priorities and everyone will forget.”

Shapira said that for the last 18 months, things were not run properly in Israel, and the death toll and infection rate prove it. But more than that, children’s education and the economy suffered, too.

“Everyone counts death, but we should be counting things that are harder to measure, like emotional damage, post-trauma – many people in Israel are scratched up,” he said. “The pandemic has been managed like a circus, and I think we are going to pay a lot for it.”