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Hadassah research head raises questions about mRNA vaccine safety

Prof. Yossi Karko, director of the clinical research unit at Hadassah-University Medical Center, has warned that the data published by Moderna and Pfizer about their coronavirus vaccine candidates is limited.

Both companies have applied for Emergency Use Authorization (EUA) from the Food and Drug Administration for their vaccines but Karko, who has been overseeing the clinical trial of Israel’s vaccine at Hadassah, said that “while they seem to be very efficient vaccines, we have to remember that this data has shortcomings.”

First, he told The Jerusalem Post, the data only tracks volunteers for one month following vaccination. While he said that “it really protects subjects quite well now,” questions remain about what happens next month and the month after.

“We do expect that the vaccine will protect us for a longer period of time, but this data is not available,” he said.

Second, Karko noted that the safety data is “very short” – only spanning the period of about two months from inoculation.

“The FDA has a mechanism of approving drugs and vaccines for emergency cases. What this means, is that the FDA has initial safety data. But if this was a usual situation, the researchers would have followed the volunteers for at least two years before the vaccine was approved,” he said.

“We need to know these reservations,” Karko said. “These things are new. There are concerns and we have to be very careful.”

He emphasized that he is not saying the vaccines are “not excellent or terrific,” but just that “we should be aware of the limitations of the data.”

Pfizer’s and Moderna’s vaccine candidates are both messenger RNA (mRNA) vaccines. If approved, these will be the first-ever vaccines of this type brought to market for human recipients.

These vaccines use a sequence of genetic RNA material produced in a lab that, when injected, enters the cells and sparks production of the viral components that subsequently train the immune system to fight the virus.

Michal Linial, a professor of biological chemistry at the Hebrew University of Jerusalem, told the Post she believes there is no cause for concern.

Linial explained that “mRNA is a very fragile molecule, meaning it can be destroyed very easily… If you put mRNA on the table, for example, in a minute there will not be any mRNA left over. This, as opposed to DNA, which is as stable as you get.”

She said that this fragility is true of the mRNA of any living thing, whether it belongs to a virus, bacteria, plant, animal or human.

She said the worry should not be that the mRNA won’t get into the cells and will stay outside, floating in the body and causing some kind of reaction.

Rather, the concern should be that if it doesn’t enter the cells, it will disintegrate and will not be effective.

She said that while Moderna and Pfizer base their vaccine candidates on new technologies, they are asking our bodies to do something they do every day: protein synthesis, the process in which cells make proteins.

In contrast to the mRNA vaccines, Karko said that Israel’s Brilife, which was designed by the Israel Institute for Biological Research, is a vector-based vaccine.

The vaccine takes the virus 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,” he said. “Then, if you happen to be exposed to the real coronavirus, the immunological response that was triggered by the vaccine will prevent infection.”

Phase I of the IIBR study was completed last week and Phase II is expected to launch in the next two weeks.

“Up to now, there are no safety concerns,” Karko said. “We are very happy with the results.”

The Phase I study included 80 volunteers: 40 inoculated at Hadassah and 40 at Sheba Medical Center.

The Phase II trial will include 960 participants and take place at nine medical centers across the country: Hadassah, Sheba Medical Center at Tel HaShomer, Barzilai Medical Center, HaEmek Medical Center, Tel Aviv Sourasky Medical Center, Samson Assuta Ashdod University Hospital, Rambam Medical Center, Shamir Medical Center and Meir Medical Center in Kfar Saba.

The Phase I study included healthy volunteers between ages 18-55. The Phase II study will include volunteers between ages 18-85, including those with some chronic diseases. The medical centers are actively recruiting for this study now.

On Monday, IIBR head Prof. Shmuel Shapira charged that development of the country’s vaccine candidate could have been further along, but it was delayed due to “over-regulation” by the Health Ministry.

Karko said that “Israel’s regulatory bodies were never asked to evaluate a vaccine” and “under the circumstances, they stood up to the challenge.”

When asked why the institute would not aim for FDA or even European Medicines Agency approval, Karko said that “IIBR does not have presumptions to produce a vaccine that is going to be commercialized.

The objective is to produce an efficient and safe vaccine to serve the citizens of Israel.”

He said that while there is excitement over the possibility that Pfizer or Moderna vaccines could arrive in the country by the end of this month, he does not believe Israel will receive enough doses for mass vaccination before the end of next year, making it even more necessary for the country to develop its own vaccine.

Moreover, Karko added that he believes coronavirus will mutate and will be with the world for more than a year and because of this, “it seems to me we will need to vaccinate more than once. Under these circumstances, having our own ability to produce a vaccine is important.”

And what about Russia’s Sputnik V vaccine, which Hadassah is vying to manufacture in Israel?

“It is a well-developed vaccine,” he said. But he admitted that the clinical process of evaluating the efficacy of the vaccine could be “deficient.”

“Until I see a publication with scientific data that has undergone peer review, I cannot really comment,” Karko added.

Source: Maayan Jaffe-Hoffman – JPost