Coronavirus vaccination: Everything you need to know

A shot in the dark? Shedding light on coronavirus vaccination and how and when Israelis will benefit from it

A woman holds a small bottle labeled with a "Coronavirus COVID-19 Vaccine" sticker and a medical syringe, October 30, 2020. (photo credit: REUTERS/DADO RUVIC/FILE PHOTO)
A woman holds a small bottle labeled with a "Coronavirus COVID-19 Vaccine" sticker and a medical syringe, October 30, 2020.
(photo credit: REUTERS/DADO RUVIC/FILE PHOTO)
People around the world are desperately waiting for the first moment when an approved coronavirus vaccine is available for the masses. They are anxiously putting their faith in a shot that they know nothing about.
With a myriad of questions and unknown entities surrounding the various options that could soon be available, here is The Jerusalem Post’s guide to everything you need to know about coronavirus vaccination and how and when Israelis will benefit from it.

What is the vaccine timeline for Israel?
Reports in recent days have indicated that some doses of the Pfizer vaccine candidate, which is currently undergoing FDA Emergency Use Authorization, could arrive in the country as early as December. However, as Health Ministry director-general Chezy Levy explained on Wednesday, wide-scale vaccination can be expected only by late spring 2021.
The first vaccine to arrive in Israel will likely be Pfizer, followed by Moderna’s and soon after AstraZeneca’s, though an announcement by AstraZeneca on Thursday - that it is likely to run additional trials - could delay the approval.
Israel also has a contract with another American company, Arcturus Therapeutics, which is now completing its Phase I human trial which showed promising results. The company has committed four million doses to Israel. Earlier this month, the company’s CEO, Joseph Payne, told the Post that the company expects to start distributing its COVID-19 vaccine candidate in the first quarter of next year.
Israel’s own vaccine candidate, Brilife, which is being developed by the Israel Institute for Biological Research, is expected to provide an interim analysis of its Phase III human trial by summer 2021 and be able to apply for emergency use approval then.
“If we assume the vaccines will be here in any quantity around April or May, and then they will be gradually distributed to specific populations,” explained Amit Asa, deputy director of the Samson Assuta Ashdod Hospital, “I would say the entire country could not be vaccinated before the end of 2021.”

Prime Minister Benjamin Netanyahu and Health Minister Yuli Edelstein visit the Teva SLE Logistic Center, which is due to store and handle the vaccines against coronavirus under special conditions, November 26, 2020 (Credit: Courtesy)Prime Minister Benjamin Netanyahu and Health Minister Yuli Edelstein visit the Teva SLE Logistic Center, which is due to store and handle the vaccines against coronavirus under special conditions, November 26, 2020 (Credit: Courtesy)
How will the vaccines be stored and distributed?
The vaccines will arrive in the country in batches and likely be stored at “vaccine farms,” central storage facilities, from where they will be dispatched to health funds and hospitals across the country.
On Thursday, Prime Minister Benjamin Netanyahu and Health Minister Yuli Edelstein visited the Teva SLE Logistic Center in Shoham, one of the country’s largest and most advanced centers for storing and transporting medicines and medical equipment. The government is likely to store some or all of the vaccines there, especially those that come from Pfizer and Moderna, which must be kept in extremely cold conditions – negative 70 degrees Celsius and negative 20 degrees, respectively.
Asa said that from there, they will be transferred to the health funds in large batches.
“The health funds are experienced in vaccinating large numbers of people in short periods of time,” he explained, noting that some 2.5 million Israelis are vaccinated against influenza each year in a matter of about two months.
He added that the Pfizer vaccine can be stored for five days in a refrigerator after being removed from the deep freeze. “Five days is more than enough to vaccinate large numbers of people. It will not be simple, but it is certainly feasible.”

Who is going to be vaccinated first?
A special committee is currently under way to determine who should receive priority vaccination. According to Cyrille Cohen, head of the immunotherapy laboratory at Bar-Ilan University, the list is likely to look similar to the flu vaccine with a few exceptions.
Medical personnel should be first, followed by the elderly and people with chronic diseases that put them at high risk of severe COVID-19. Next would be people who come into regular contact with large groups of people, teachers and prisoners, followed by pregnant women and babies, as well as senior center staff. Finally, everyone else will get access.
Looking at the eligibility for the largest Phase III clinical trials, there are no studies that include volunteers under the age of 12 or pregnant women. As such, Cohen cautioned that there could be a delay in distributing the vaccine to these populations until safety data are available. Vaccines should not be used for people not included in the clinical trials, he noted.
Cohen added that it is possible that the public will be able to choose between the various vaccines, but this will likely depend on availability. Moreover, he said that as the data are further evaluated, it could be discovered that certain vaccines are better for certain populations. For example, AstraZeneca’s potential COVID-19 vaccine produced a strong immune response in older adults, the data showed.
A medic of the regional hospital receives Russia's "Sputnik V" vaccine shot against the coronavirus disease (COVID-19) in Tver, Russia October 12, 2020.  (Credit: REUTERS/TATYANA MAKEYEVA/FILE PHOTO)A medic of the regional hospital receives Russia's "Sputnik V" vaccine shot against the coronavirus disease (COVID-19) in Tver, Russia October 12, 2020. (Credit: REUTERS/TATYANA MAKEYEVA/FILE PHOTO)
Will people willingly be inoculated?
More than half of Israelis (52%) said they “think they would not” or are “convinced they would not” be vaccinated against the coronavirus if a vaccine becomes widely available, according to a survey published earlier this month by the Israel Democracy Institute.
Asa said that he believes these statistics could change if the Health Ministry launches a marketing campaign already now to convince the population that these vaccinations are approved by the most stringent regulatory institutes.
“I have heard people in Israel making comments like, ‘I will not be the first person to get vaccinated.’ That is ridiculous,” said Prof. Jonathan Gershoni of the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University. “There is no vaccine that we are going to start using to vaccinate the Israeli public before it has been used on millions of people in its country of origin.”
Asa added that his hospital is currently recruiting for IIBR’s Phase II coronavirus vaccine trial and “hundreds of people are requesting to be the first candidate. I don’t think we will have a problem.”

How many people have to take it to make the vaccine effective?
There is no magic percentage, said Cohen, explaining that the level of herd immunity will be based on the efficacy of the vaccine and the number of people who take it.
“If you believe you will reach herd immunity when you get 70% of the population immunized naturally or using the vaccine, that means you need at least 75% to 80% of people to take a vaccine that is 90% effective,” he said.
But he added that even if lower numbers take the vaccine in the first months, after a few weeks – if few or no side effects are seen – more people will ask to get vaccinated.
“You cannot talk about herd immunity like you need to reach 70% and anything below will not work – it is just not true. The more people get vaccinated, the less COVID we will have,” Cohen stressed.
Gershoni added that by law the government will not be able to force anyone to take the vaccine; however, it would be possible to require a coronavirus vaccine to get on an airplane or enter certain countries.
“It would not seem outrageous if I was told that before I can get on a plane I have to be able to show that I have been vaccinated,” he said. “Now, I have to prove I am corona negative by doing a PCR test.”
Is Israel done purchasing vaccines or will there be more?
Asa said that there will be more companies announced in 2021, and there might even be more contracts signed that have not yet been made public.
Cohen, who sits on the Advisory Committee for Clinical Trials of Coronavirus Vaccines through the Health Ministry, said that it was made public that Israel is in talks with Johnson & Johnson.

How do viruses and the vaccines against them work?
There are two types of vaccines, Gershoni explained: hardware and software.
Hardware vaccines contain physical components of the structure of the virus and represent all the vaccines that exist today and are taken by human beings worldwide.
“In the past, I referred to viruses as if they are a disk-on-key,” Gershoni explained.
A flash drive is packaged information or memory inside a plastic or other case. For the information to get inside the computer, it must be inserted into a compatible corresponding socket.
The same is true for viruses: They have genetic information packaged in some sort of encasement. Included in the virus’s protein coat are select proteins, often referred to as spike proteins, which function like the USB plug of a disk-on-key. The spike protein binds to a corresponding receptor on a cell that is being infected. Only when a viral spike protein engages and binds – only when it is introduced into the receptor – can it infect the cell.
Hardware vaccines constitute the structures of the virus: the coat protein, including the spike protein.
There are three types of hardware vaccines.
The first is “killed” or inactivated viral vaccine, which is when a specific virus is killed with chemicals. The “dead” viral particles are then introduced into the body. Even though the virus is dead, the immune system can still learn from its antigens how to fight live versions of it in the future. The flu vaccine is an example.
The second is a live “attenuated” vaccine, one in which a living virus has been modified or weakened so that when it is injected into a person it does not cause disease but still elicits an immune response. The measles vaccine is an example.
Finally, a subunit vaccine is when only the protein components of a virus that are capable of inducing a protective immune response are leveraged. An example of this is the Hepatitis B vaccine, which is so safe it is administered to babies at birth, even before they leave the hospital.
Gershoni said there are some companies working on these more conventional vaccine candidates against COVID-19, including Maryland-based Novavax, Inc. and the French pharmaceutical company Sanofi. Both of their vaccines are subunit vaccines that contain the viral spike protein. Novavax is in the midst of its Phase III trial, and Sanofi is expected to start its late-stage trial next month.
“I would expect Israel will try to sign for these,” Gershoni said.
The vaccines that are all the rave now are software vaccines, those in which scientists take the blueprint of the virus – just the RNA or the genes corresponding to spike protein – and inject that in a palatable and effective way into the body. The cells then synthesize the viral protein and mount antibodies against the viral spike.
On January 9, 2020, the entire genome of the novel coronavirus was published by the Chinese. The size of the genome is 30,000 bases of RNA; coronavirus is an RNA virus. The size of the specific gene that codes for viral spike protein is only 12% of the genome.
As such, small snippets of the novel coronavirus genes that correspond to the spike protein are what is being injected.
“Under these circumstances, you have no chance of causing the disease,” Gershoni said.
One modality of a software vaccine is to take RNA that corresponds to the spike protein and encapsulate that RNA in some sort of a mixture of lipids so as to raise a response to the area of the injection – this is like Pfizer and Moderna.
Another method is to deliver the gene for the spike protein via another virus that infects human cells but does not cause any noticeable or harmful disease.
“If we take a virus like that and manipulate its genes and swap some of the genes of the viral vector with the gene for the coronavirus spike, when such viral vectors infect our cells they are manipulated and produce the coronavirus spike protein, which then stimulates the production of antibodies against coronavirus,” Gershoni further explained. This is what AstraZeneca, Johnson & Johnson and Moscow’s Gamaleya Research Center are doing.
In other words, all of the vaccine candidates that Israel has access to now are software vaccines.
“There are no software vaccines that have been previously approved by the FDA and used in humans,” Gershoni stressed – not Moderna and not AstraZeneca.
Vials with a sticker reading, "COVID-19 / Coronavirus vaccine / Injection only" and a medical syringe are seen in front of a displayed Pfizer logo in this illustration taken October 31, 2020 (Credit: REUTERS/DADO RUVIC/ILLUSTRATION/FILE PHOTO)Vials with a sticker reading, "COVID-19 / Coronavirus vaccine / Injection only" and a medical syringe are seen in front of a displayed Pfizer logo in this illustration taken October 31, 2020 (Credit: REUTERS/DADO RUVIC/ILLUSTRATION/FILE PHOTO)
So how did they get approved so quickly?
The emergence of the first cases of COVID-19 occurred in December 2019. As noted, the Chinese were able to rapidly isolate the virus by January 9, 2020. With today’s knowledge in genomics and bioinformatics, the moment that scientists saw the sequence, they were immediately able to begin the research and production of software vaccine candidates.
“The accelerated speed should not be interrupted as dangerous as far as safety is concerned,” Gershoni said. “All the companies are conducting Phase I, II and III human trials. No corners have been cut.”
Rather, he said, the companies are taking an enormous financial risk by running clinical trials in parallel and producing vaccines even before they are fully approved.
“Not all the vaccines may be safe” that are being developed, he further explained. “But I do believe that all those vaccines that are approved by the FDA should be considered safe.”

Will they have any short-term side effects?
The short-term side effects of these vaccines will likely be tiredness, soreness at the site of injection, redness or inflammation, maybe even a slight temperature – all symptoms that are manageable with Tylenol.
“What we want to try to avoid is a vaccine that causes dramatic side effects,” Gershoni said, admitting that because the vaccine will be tested on tens of thousands of people rather than millions, “there is no way that you can tell what kind of side effects are rare and could appear in one in a million cases.”

What about long-term side effects?
Cohen admitted that because mRNA vaccines are new, there might be some “undesirable reactions” that will be discovered only in the long term, though there is no proven evidence.
These “very rare” reactions could include local and systemic inflammatory responses that could perhaps lead to autoimmune conditions; the bio-distribution and persistence of the induced immunogen expression; and possible development of autoreactive antibodies, as have been reported by the National Institutes of Health.
However, Michal Linial, a professor of biological chemistry at the Hebrew University of Jerusalem, told the Post in a previous interview that 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 is 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 plant, bacteria, virus or human.
Cohen said that “our bodies are full of RNA,” and these vaccines are asking them to do something they do every day: protein synthesis, the process where cells make proteins.
“There can always be long-term effects – not just of these new mRNA vaccines, but in general,” said Cohen. “But remember, we don’t know yet that there won’t be long-term effects of COVID-19.”
“Which is more dangerous: COVID-19 or being vaccinated by something that raises viral response to spike protein?” Gershoni asked. “My sense is that these presentations of the viral spike are much safer than having to experience the disease.
“Comparing vaccination to disease – there is no comparison,” he continued. “The only thing you can argue is that you would rather play Russian roulette and hope you don’t get infected.”

Hadassah-University Medical Center doctors administer the country's COVID-19 vaccine (Credit: HADASSAH)Hadassah-University Medical Center doctors administer the country's COVID-19 vaccine (Credit: HADASSAH)
Are vaccinations safe in general?
In general, FDA-approved vaccines are “remarkably safe,” a study by researchers from Tel Aviv University and Sourasky Medical Center showed over the summer.
The group, led by Dr. Daniel Shepshelovich of TAU’s Sackler Faculty of Medicine, studied 57 vaccines that were approved by the US Food and Drug Administration between 1996 and 2015 that yielded 58 safety-related issues associated with 25 of them – most of them identified through the FDA’s Vaccine Adverse Event Reporting System. Those that were identified were of limited clinical significance, rare and not life-threatening, the study found.
In only one case in the last 20 years was a vaccine pulled off the market. The RotaShield vaccine for rotavirus was removed within months of approval after it was found to have mild bowel side effects in one out of every 5,000 to 10,000 people who took it.
The conclusion: Vaccines are very safe – much more so than drugs and medical devices, whose side effects are many and more dangerous, according to the study, Shepshelovich told the Post in July when the study was published.

People who tested positive for COVID-19 in the past – will they still need to be vaccinated?
In theory, if people have recovered from the disease, they don’t really need to be vaccinated, because they presumably have natural immunity. The challenge, said Gershoni, is that doctors still don’t know how effective or long-lasting that immunity is.
“We may learn that natural immunity is less robust than we had hoped, and therefore vaccination [of people who had COVID-19] plays a very good role in boosting immune response, and that might be helpful,” he said.
Gershoni suggested that, over time, it could evolve that people who had the virus will take a booster shot to ensure strong immunity.

What questions remain?
Even as the vaccines are approved, several questions will remain unanswered. These include the sustainability and the immunogenicity of the vaccine – which could be evaluated only in the longer term.
It is also still unclear whether the virus will mutate and modifications will need to be made to the vaccines, even perhaps as often as annually. However, in comparison to influenza, it is understood that coronaviruses in general are more genetically stable.

Will vaccination mean the end of the pandemic?
“I am certain that we are not going to go back to where we were in November 2019,” Gershoni said. “That is because we experienced a traumatic pandemic and adopted various behavioral patterns.”
However, wide-scale immunity will allow people to resume normal activities and reopen the economy in a way that the public has not experienced in more than nine months.
As Edelstein said on Thursday: “It is not just a light at the end of the tunnel but a path we are on.”•