What happened to Israel’s COVID-19 vaccine?
BriLife was hailed as a major breakthrough, but delays continue to pile on
Israel’s coronavirus vaccine candidate will not be available at least until the end of the calendar year, despite original hopes that there would be a blue-and-white shot approved by summer, The Jerusalem Post has learned.
The Phase II trial for the Israel Institute for Biological Research’s BriLife vaccine, which was slated to conclude by Passover 2021, has been paused for two months while scientists prepared a higher dose of the vaccine to include in the study. Those in charge of the trial at their hospitals say they expect to restart only in a week or two.
In the meantime, volunteers have been waiting and the timeline for launching Phase III – the final step required before seeking approval – has moved further into the future.
IIBR began working on a coronavirus vaccine back in late February or early March 2020 at the suggestion of Prime Minister Benjamin Netanyahu, giving the country high hopes that it could be the solution to the coronavirus crisis.
IIBR operates under the auspices of the Prime Minister’s Office and works closely with the Defense Ministry.
There was so much faith in Israel’s ability to produce a vaccine that even the founder of the anti-Israel Boycott, Divestment and Sanctions movement, Omar Barghouti, informed his followers that if Israel finds a vaccine for coronavirus, boycotters could take it.
IIBR got off to a slow start, due to what the institution’s director-general, Shmuel Shapira, described at the time as overregulation and bureaucracy. But by late November, researchers had completed Phase I of the trial and shown the BriLife vaccine to have few side effects and no severe ones.
The vaccine’s Phase II trial was approved and kicked off in December, around the time that the first vaccines arrived in Israel. The country’s stunning, rapid-fire vaccination campaign made it difficult to recruit volunteers, some of whom would naturally be given a placebo instead of an active vaccine.
But the latest delay was due to a shift in the trial’s protocol, Prof. Yossi Caraco, head of the
Clinical Pharmacology Unit at Hadassah, told the Post. He is overseeing the trial at his hospital.
“Up until now, we have been using three doses – low, medium and high doses,” Caraco explained. “The low dose does not induce sufficient response. While all subjects enrolled in the low dose [arm of the trial] are still being followed up, they all have been encouraged to get a vaccination from the commercial vaccine available to all Israeli citizens.”
Doctors were forced to eliminate around 200 study participants who received a low dose from the study, leaving them with only around 500 volunteers of the close to 1,000 who were supposed to be included in Phase II. Another 200 people then had to be recruited for the replacement arm, a “higher-than-high dose,” Caraco explained, “that we believe might even be better.
“We have noted that there is a correlation between the dose of the vaccine and the extent of the immunological response,” he continued. “Even though we were quite satisfied with some of the doses, we do expect the higher dose may improve the results we are seeing up until now.”
Caraco said he could not provide any details about the vaccine’s efficacy to date and instead just could say that “the results are promising.”
But getting this extra top dose took an unexplainably long time, Prof. Eytan BenAmi, head of early phase clinical trials at Sheba Medical Center, told the Post.
“It took some time for the institute to have it made,” he said. We finished recruiting and then we waited for them – for the new vaccines to be ready.”
He said he does not know why it took so long.
The Defense Ministry denied that the delay was its fault. A ministry official told the Post that “the time lines have changed due to circumstances not dependent on the institute,” adding that Phase II of the BriLife clinical trial is “progressing well” and that the institute is working within its budget.
Last month, during this hiatus, Shapira announced that he would be stepping down from his role this May, and to
date no replacement has been selected.
Shapira had expressed frustration at the lack of support for IIBR and the cumbersome bureaucratic hurdles, telling the Knesset in November that BriLife could have been further along if not for overregulation.
The study’s extension frustrated volunteers who didn’t know whether to wait for a jab from the blue-and-white vaccine or go ahead and seek the alternative Pfizer vaccine. Lack of clear communication from hospitals and IIBR made the situation worse.
Jerusalemite Daniel Laufer, screened by Sheba for the study in February, received a follow-up phone call only in April.
This is more progress than Yokne’am’s Jay Ross has made, who over the past few months has reached out to IIBR and others to sign himself and his family up to get the jab.
“We saw that they were having the trials, and we tried to send them an email to get into the first trial, and we never heard back,” Ross told the Post. “Then we offered to do Phase II and III, and no one ever responded to us.”
Ultimately, Ross had to travel to the US to care for a sick
relative and got the Johnson & Johnson vaccine. But his wife and older children would still like to take part if someone would contact them.
“The government has fallen extremely short, I believe because of putting politics above the population,” Ross said about the process, knowing that IIBR is funded by the state. “It makes no sense why they would take so long to move forward. It looks like Israel just dropped the ball.”
He said that “Israel is one of the leaders in the world in technology and medical breakthroughs, and I don’t know why they have no interest in developing this vaccine – at least it seems that way.”
But Caraco defended the trial and said that these setbacks are not unusual in clinical settings.
“Since Israel has had the vaccines available since December, it would not be responsible from our side to endanger and put at risk subjects just to move faster,” Caraco told the Post.
“Even though the original objective was to produce vaccines that would be helpful in order to overcome the disease, this has been achieved through getting the commercial vaccines of Pfizer,” he said.
But he added that recent research indicates that vaccinating against coronavirus will be similar to the flu in that people will need to be inoculated every year. Hence, the vaccines could still be put to use in the country.
And, if not, “of course they can be used to vaccinate other countries that need a vaccine.”
Netanyahu said on Tuesday that he believes Israel will roll out another vaccination campaign in about six months, “so get your shoulders ready and your children because we estimate that by then vaccines will be approved for children.”
Caraco said that the first two months of the top-dose part of the trial “are the most important ones,” and if the results are good, they could already begin designing Phase III.
The final phase would need to take place outside of Israel because it requires the participation of 30,000 to 40,000 volunteers and must be undertaken in an area that still has high infection. Israel’s mass vaccination campaign has left few eligible volunteers and continues to bring down morbidity.
WHILE WAITING for IIBR, Israel inoculated more than five million citizens at a cost of NIS 2.6 billion. This week, it contracted to purchase another more than nine million doses from Pfizer and another seven million doses from Moderna at a cost of around NIS 1.5b.
Israel also prepurchased some 10 million doses of the AstraZeneca vaccines, which it is now trying to reroute to another destination.
In contrast, Israel has invested only NIS 175 million on BriLife, the Defense Ministry told the Post.
Health Minister Yuli Edelstein defended the ministry’s vaccine procurement process and has told the public that there has been no wasted money nor any wasted vaccines.
“So many months ago, my instruction was not to put all the eggs in one basket,” Edelstein said Tuesday. “That’s what we did.”
THE BRILIFE vaccine is different from the Pfizer or Moderna vaccines, which are messenger RNA vaccines.
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 a disease by itself. VSV does not infect humans. Instead, the body recognizes the spike protein that is expressed on the envelope and begins to develop an immunological response.
“It’s like getting a virus like coronavirus without getting the disease,” Caraco said. “Then, if you happen to be exposed to the real coronavirus, the immunological response that was triggered by the vaccine will prevent infection.”
He said that considering the level of neutralizing antibodies produced by the vaccine, “the initial results are promising.”
Ben-Ami added that there have been no safety issues or concerns.
BriLife also does not require being stored in extreme temperatures, which could make it easier to distribute worldwide.
Caraco said that three South American countries – Brazil, Mexico and Argentina – are in advanced stages of negotiations to help run the Phase III trial and purchase the vaccines if successful. These countries continue to have high levels of infection and low access to vaccines.
Israel has the ability to produce 15 million doses of the vaccines and would otherwise have to develop a vaccine manufacturing plant or outsource production. Yeroham Mayor Tal Ohana said the city has been working to establish such a plant since December 2019, even before coronavirus.
SHAPIRA PREVIOUSLY explained that the “Bri” in BriLife is the first part of bri’ut, the Hebrew word for health, and the “iL” stands for Israel, connecting to “Life.”
“The Biological Institute’s vaccine is intended to ensure the State of Israel full independence in the development, production and supply of vaccines to all its citizens, without dependency on foreign entities and for the long term,” the Defense Ministry told the Post.
Ben-Ami said he believes continuing with the vaccine trials regardless of delays or other vaccine purchases is “strategically important.
“We need to be more independent in terms of the vaccines,” he told the Post, “and, of course, there is a shortage of vaccines almost anywhere in the world. If we can contribute to that, it would be a very large benefit.”