Prof. Jonathan Gershoni has been studying viruses and immune systems since the early 1980s. Until half a year ago, these subjects didn’t interest the general public. Now they feature in newspaper headlines, social media posts and living-room discussions. “I feel as though I’ve been given the stage after 40 years of writing a play,” says Gershoni.
Gershoni is realistic, but an optimist too. He is convinced that in the end there will be a coronavirus vaccine. But anyone hoping for an imminent return to routine should lower their expectations. “I don’t think we’ll have a solution in the form of a vaccine before [fall] 2021. If I’m wrong and it’s earlier, so much the better. In my opinion, there’ll be an effective medicine before there’s a vaccine.”
We must realize that we’ll be living for quite a while with a pandemic. “What does that mean for Israelis? More humility. To recognize that we’re confronting a force of nature. There’s no negotiating with the virus. Israelis, like the rest of the world, are confronting a terrible disease. We need mature, serious, modest, responsible and effective leadership, based on science and knowledge and a correct economic approach,” stresses Gershoni.
In his opinion, a “pandemic routine” is entirely possible. “There are diseases for which there’s no vaccine and we’ve learned to deal with them, like AIDS, and it’s easier to wear a mask than a condom. If Israelis have learned not to pick anemones, we’ll know how to deal with the coronavirus on a daily basis, without disrupting our entire lives.”
Frequently in the course of our discussion, Gershoni expresses anger at disinformation, ignorance and errors in the media, among the public and even among decision makers. “We hear experts who say the virus has mutated or that the virus has returned with greater intensity. That infuriates me. The virus hasn’t changed. It’s neither more severe nor weaker. It’s here, and we have to learn to live with it.”
In the same breath, he takes pain to explain that he and other experts don’t have answers to all the questions. Many aspects of the coronavirus and the immune response to it remain a mystery.
Gershoni, a professor of molecular immunology and virology at Tel Aviv University’s Faculty of Life Sciences, has studied rabies, AIDS and flu viruses, as well as the coronaviruses responsible for the SARS and MERS outbreaks this century. In 2016 he developed a method of vaccination against coronaviruses that he patented in the United States.
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One of the questions preoccupying researchers is whether a person infected with the coronavirus develops natural immunity that will protect him from future contagion. What do we know about that?
Gershoni: “There are contradictory reports. There are four kinds of coronaviruses that attack humans, aside from SARS, MERS, and SARS CoV-2, which causes COVID-19. We’ve been familiar with two of the four since the 1960s, and they cause a third of all colds – a bit of sneezing, fever and coughing, and we recover. We can become ill and recover from the coronaviruses of the common cold, and fall ill again the following season. That’s a fact.
“Generally speaking, when we’re infected with the coronavirus for colds we develop enough of an immune response to clear the virus from the body and we recover. But for reasons that are unclear to me, the response is not necessarily strong enough to prevent contagion the next time we meet the virus.
“With COVID-19 we’ve seen that among those who recover, an effective level of antibodies is produced that neutralize the virus, and that’s good. However, there are reports that in some patients the antibody response weakens over time, which is of course the opposite of what we would like. It’s a somewhat worrisome indicator, because the response among those people is not stable for long. We have no way of knowing who will develop a stable and ongoing protective response and who won’t.”
It’s true that one can contract influenza repeatedly, even if vaccinated, but that’s because the flu virus undergoes repeated variations and mutations. Even if we have been vaccinated against one type, we can be infected by a new one the following year. Coronavirus, by contrast, doesn’t change significantly.
Why is that?
“Viruses are tricky. They evolve and acquire features that give them an advantage over the body’s immune system. That’s why it’s possible – and this is only a theoretical speculation – that the coronavirus developed in such a way that it arouses a limited immune response and leaves the stage before the immune system develops an effective immunological memory.
“In that sense the viruses have a certain advantage. For them ‘I did what I did, I multiplied as much as I multiplied, I spread as much as I could and I’m finished for the season. But wait, I’m coming back next year.’ It’s possible that the virus developed in that way to become a weak immunogen (a foreign body that arouses an immunological response) – the kind that disappears before we’re able to develop an immunological memory that remains stable for years, and thanks to that it succeeds in infecting more people annually.”
Although there is no clear evidence either way, Gershoni and other experts still believe that the body develops effective protection against the coronavirus, which prevents additional contagion. In other words, it may not be possible to be infected by the coronavirus twice, at least not within a short period of time, and if so that’s rare.
In addition, experts interviewed in The New York Times believe that although the level of antibodies may weaken in certain cases, in most cases the body develops a sufficiently effective immune response to protect itself from renewed contagion. Among other things, that happens thanks to the immune system’s T cells.
As opposed to antibodies (which are created by B cells), T cells do not prevent contracting the virus, but they do identify cells in the body that have been infected and destroy them. That’s how they halt the spread of the virus in the body and reduce the severity of the symptoms.
What are the implications of all that for our ability to develop a coronavirus vaccine?
“I’m sure there will be a COVID-19 vaccine. I assume that it will be effective and I think it won’t need to be revised every year. As scientists we have a right not to play according to the rules of nature, of biology, of the virus. We can do what we want. The vaccines being developed today can do something that the virus doesn’t do: We can distill the envelope (E) protein of the coronavirus at a high concentration, vaccinate someone and stimulate an initial response that focuses on this protein. If necessary – and that’s common in the vaccine world – we can give a booster shot after a month or half a year.”
How will that help?
“It renews the stimulation, strengthens the immune response and establishes an effective and efficient memory. That way, in the event of a real attack – an encounter with a violent coronavirus – the antibodies that were created as a result of the vaccine will immediately say ‘I know this virus,’ and thanks to the memory, will activate a strong response that will check the disease.
“Incidentally, I also find an interesting twist in that. Usually anti-vaxxers claim that natural immunity is better than vaccines produced by pharmaceutical firms. Their philosophy is that the world of medicine is a conspiracy to make a profit maliciously. It’s possible that here there will be a unique and interesting – and even very encouraging – situation, that proves that artificial vaccines are more effective than the body’s natural immunity.”
Companies are promising vaccines by the end of this year or the beginning of next year, and are publishing results that look promising.
“They’re constantly releasing snippets of information to the public, but the problem is that the public doesn’t see the full picture. Israelis don’t care about the findings of the stages of the clinical trials, Phase I, II or III. They’re interested in one thing: When can I roll up my sleeve, get an injection, hug my grandchildren and fly abroad? When will we return to normal life?
“But if you look at the details of the approval of the clinical trials of the vaccine developed by the pharmaceutical company Moderna, for example, they’re scheduled to complete phase one in October 2022. Not exactly what we thought, right? Moreover, they conducted safety trials to check in subjects aged 18-55. At the moment the safety or efficacy of the vaccine for babies or 70-year-olds like me, isn’t clear. Meanwhile it’s impossible to know the extent to which the vaccines in development will be effective in preventing contagion and for how long, or whether there will be a need for booster shots.”
Companies are trying to shorten the development process and Russia announced it would begin producing a vaccine without phase three trials. What does that say about the safety of the vaccines?
“It’s impossible to know what the side effects of the vaccine will be from Phase I trials, which may appear after 12 months, when only five months have passed. There are things that are unavoidable, and where you can’t cut corners. When we plan to vaccinate large parts of the global population, we can’t compromise on safety. The job of pharmaceutical companies, governments and regulators is to instill confidence that they didn’t compromise and that the product that they’re going to inject into a healthy person is not only effective but safe as well, without side effects and without risks.”
If there are problems with the vaccine, that could provide tremendous support for anti-vaxxers.
“Historically, there have been mishaps with vaccines. With Jonas Salk’s first polio vaccine, for example, a company called Cutter vaccinated children in 1955 with a vaccine that had not been neutralized according to the protocol. Hundreds were infected and contracted polio. A few years ago Sanofi vaccine recalled a vaccine it developed against dengue fever.
“With dengue, and perhaps with the coronavirus too, there’s a phenomenon called ‘antibody-dependent enhancement.’ If you’re infected for a second time, it can cause the antibodies you developed the first time to exacerbate the illness. So imagine that there’s a vaccine against COVID-19, but it turns out that those who are vaccinated will develop a more serious illness. That’s why we have to use discretion and avoid haste.”
Is it possible to shorten processes?
“It’s hard to shorten processes but maybe, due to the urgency of the situation, we can make an exception. I suggest, although it’s not exactly in accordance with the rules of ethics, taking several healthy young people who were vaccinated in trials and expose them in a controlled way to the coronavirus.
“It’s a daring move, but these are unusual times. We would be able to examine the degree to which they’re protected from the virus, and the connection between the level of antibodies and protection from the virus. Such trials could teach us which parameters guarantee effective protection and could help in the development of an effective vaccine.
“We could also shorten manufacturing times, and that’s what they’re doing now, in effect. Companies such as Johnson & Johnson and Moderna have begun producing doses of their vaccines even before they’ve been proven to be effective and have received U.S. Food and Drug Administration approval. In an ordinary situation, a company won’t start manufacturing a product until there’s proof and permits. But here the U.S. government is saying ‘it’s at my expense’ and sharing the risk.”
Israel has signed agreements with Moderna and Arcturus to provide it with future vaccines and is in contact with other companies. What about the vaccine being developed by the Biological Research Institute in Nes Tziona?
“I wouldn’t assign a government body the job of preparing a vaccine. I want a vaccine that was developed and checked by a company with proven skills and experience in the mass production of vaccines. This isn’t the time the institute has been ‘ordered’ to save Israelis. In general, I find it hard to accept the idea that the facility has suddenly become public knowledge. I’m from the generation that wouldn’t have dared mention the mere existence of the Sayeret Matkal commando unit, much less the Shin Bet security service and the Mossad.
“It’s not certain that the institute has the tools and experience to develop vaccines and treatments. And even if it has the tools – and I respect the researchers and their capabilities – then certainly nobody should issue declarations. If I were at the institute I would be horrified by politicians’ remarks, whether it’s Yamina MK Naftali Bennett or [Prime Minister] Benjamin Netanyahu. I find Netanyahu’s arrogance very hard to take.”
So what would you recommend to the government?
“I think it’s responsible policy to try to guarantee access to vaccines when the time comes, understanding that there may be a lot of competition. My recommendation is that we need serious, more modest and effective professional leadership, with a plan and a vision. I wish Prof. Ronni Gamzu support and the ability to operate effectively without being disturbed. The government imposed harsh restrictions on the people, we achieved results and dropped to almost zero cases of contagion.
“But [Netanyahu] didn’t know how to leverage the high price paid by the public. He told Israelis to have fun and sent them off to drink beer. There was no plan and the politicians had no idea how to guide us in living with the coronavirus without igniting a second wave. Our success to date is due to ordinary citizens trying to adapt their behavior to an impossible lifestyle, and to the devoted doctors and nurses who administer effective treatment to their patients and who are collapsing under the burden.”