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Should we get a third vaccine shot? The answer isn’t so simple

By Abigail Klein Leichman

Dr. Ronald Ellis, vaccine industry consultant. Photo: courtesy

With rising Covid-19 cases caused by the Delta variant and concerns about how long the Pfizer-BioNTech vaccine remains effective – and how effective it is against Delta – the Israeli government decided on July 29 to make a booster shot available to every Israeli over age 60.

Israel has followed an aggressive vaccination policy from the start. A third Pfizer shot already has been given to immunocompromised people, and initial doses to children between 12 and 15.

ISRAEL21c turned to Jerusalem-based expert Ronald Ellis for answers to some of the most pressing questions about the Covid-19 vaccine and booster shots.

Ellis played key roles in developing five vaccines currently accounting for about $8 billion in annual sales worldwide, is a consultant to the industry and editor-in-chief of the international journal Human Vaccines & Immunotherapeutics.

Q: The Israeli Health Ministry is finding a decline in the effectiveness of the Pfizer Covid-19 vaccine to prevent infections and symptomatic illness. Does this mean Delta is resisting the vaccine?

Delta is one in a long line of variants. We will see more of them over time. To date, there isn’t a single variant that is totally resistant to vaccine-induced antibodies. It may take more antibodies to neutralize these variants than the original Wuhan [Alpha] variant, but the virus doesn’t totally escape them.

Q: Why do we see fewer instances of serious Covid-19 among vaccinated people who do get infected?

The vaccine may not stimulate production of enough antibodies to stop the virus cold; the virus may get in and start replicating. That will stimulate immune memory, which will greatly increase the level of antibodies within just a few days, and in most people that will prevent severe disease – and worse.

Q: So, the Pfizer vaccine is still doing its job?

With Wuhan, the vaccine was up to 90% effective against infection and 95% effective against symptomatic disease. With Delta, it looks to be about 30-40% effective against infection and 90% effective against disease. During the last two months, the number of serious cases has gone up less than tenfold despite the number of cases going up more than 100-fold. So, the vaccine is doing the job. In general, vaccines prevent disease much more than they prevent infection.

Q: As soon as Pfizer released data showing “reasonable safety” for 12- to 16-year-olds, Israel began an aggressive campaign to inoculate this population. Are you in favor of this policy?

In terms of the balance between benefit and risk, yes. There are rare reports of mild myocarditis or significant side effects in teens. On the other hand, there are serious Covid-19 cases that arise even among teenagers, and serious side effects that persist after infection or disease.

There’s also the issue of altruistic vaccination – vaccinating teens not only to protect them but also to keep the level of coronavirus down in the community and in the vaccinee’s family.

Q: What about vaccinating younger children? Pending clinical trial results, the United States may approve vaccinating under-12s in the coming months.

How young you go depends on the disease statistics. If the vaccine proves safe in ages nine to 12, then depending on the amount of virus circulating we probably want to do it.

However, 12- to 16-year-olds have larger lungs than little kids. Because they’re exhaling larger volumes of air, they are more likely to infect somebody than is a small child exhaling smaller volumes.

Also, infection is spread by droplets and gravity gradually pulls them down to the ground. A 16-year-old is exhaling at a vertical level to adults, whereas two-year-olds are exhaling near an adult’s legs. So the bigger risk is from this taller kid with a larger volume of air, and that is also one reason vaccinating teens may have a higher altruistic effect for adults.

Sheba Medical Center nurse Lina Ahmad vaccinates President Isaac Herzog, 60, while his wife Michal waits her turn and Prime Minister Naftali Bennett (right) looks on. The Herzogs were first in the world to receive the third Pfizer vaccine as a booster, on July 30. Photo courtesy of Sheba Medical Center.

Q: Israel was the first country to begin giving booster doses of the vaccine to immunocompromised citizens. Many of these people did not develop antibodies in response to the first two doses. Was this a sound decision?

We won’t know for certain until we see if it has the desired effect. It is hard to do clinical trials in immunocompromised patients, so it seems a reasonable benefit-to-risk balance to boost the most vulnerable populations as the Delta variant spreads. We must make decisions in real time even though all our decisions will not be perfect decisions.

Let’s remember that the vaccine is being given under emergency use authorization – to this day, the FDA still hasn’t given formal approval to any Covid vaccine. We are only learning now about how Covid vaccines boost and how long antibodies last. It will take a couple of months to see those results and any adverse effects.

Q: On July 29, the Israeli Ministry of Health decided to offer boosters for those over 60. Is it wise to start giving everyone third shots?

We’re only six months post-vaccination for most people, and most are retaining protective levels against Covid-19 disease. The decision to boost should be based on decay of antibodies. And the longer you wait, the stronger the boost you get. If you boost too many times, your immune system might not respond as well.

In addition, since there will be future variants, it might not be reasonable to boost again each time there is a new one, and it might be difficult to “sell” people on the idea of too many boosters.

However, in light of the recent very large increase in Delta infections, I feel that a benefit-risk analysis clearly favors getting the booster shot in terms of how the booster significantly raises antibody levels.

This is taking a bit of a chance in that we are the first country to recommend boosters, and we did so ahead of an FDA decision in the US.

We need to monitor safety in individuals post-booster. We also should continue to take other preventive measures, such as indoor masking.

Editor’s note: Health Ministry spokesman Dr. Asher Shalmon told ISRAEL21c on August 1 that antibody testing for those over 60 is not being recommended as a basis for deciding whether to get boosted because the correlation between antibody levels and immunity still is uncertain.

Q: Do you think we’ll need booster shots yearly, like with flu shots?

Corona is different from the flu because it’s not escaping the antibodies from the previous vaccine as flu virus does. With flu, the surface of the virus changes, or “drifts,” so the old vaccine doesn’t work well and you need a new composition.

With corona, the question is what do you boost with? The vaccine developed for Wuhan might boost antibodies against Delta and against the future hypothetical variant Epsilon. Or it may work only against Delta if Epsilon has drifted onto a different branch of the coronavirus tree. We need lab and animal studies to test whether we have to boost against Wuhan, Delta, Epsilon, or a combination.

The right policy [for most healthy people] is to wait maybe a year or so from the initial vaccination. If you boost for Delta, and Epsilon comes along in six months and it’s resistant to the Delta-induced antibodies, what do you do?

Time will tell if there will be annual boosters.

Editor’s note: The Israeli Ministry of Health is recruiting 1,000 families to participate in a study to evaluate what segments of the population would most benefit from a booster dose, and when. 

Q: If you got the Pfizer vaccine, will you have to get a Pfizer booster as well?

Clinical studies are already under way on people already vaccinated to see how well the different vaccine types boost each other. They all express the same protein from the virus although in a different form.

A booster re-exposes the individual to the antigen, so I expect that most vaccines will boost most other vaccines. But you need the data to be sure, and some combinations might present unexpected safety issues.

Q: What about the issue of vaccine equity?

Corona is a worldwide problem. Should wealthy countries give lots of booster shots and vaccines to children, or should they send those doses to impoverished areas that don’t have enough for everyone? From an ethical health equity point of view, it’s a tough issue and will influence how vaccines are distributed and used.

This article is reprinted from Israel21c.org.

Will an Israeli vaccine be the solution to new variants?

By Abigail Klein Leichman

Several Covid-19 vaccines under development in Israel hold out promise for their ability to protect against variants of the virus that are challenging existing vaccines.

Back in May 2020, research groups across the world were racing to formulate vaccines against the SARS-CoV-2 coronavirus. Realizing it was not going to win that race, Israel purchased millions of Pfizer-BioNTech and Moderna mRNA vaccines from the United States and led the world in getting eligible citizens vaccinated.

Israel was the first country to offer the vaccine to 12 -to 15-year-olds and to offer booster shots to immunocompromised people and those over 60.

However, domestic inoculations still to come may become significant as primary vaccinations or as boosters against highly contagious variants of the virus.


U.S.-based NRx Pharmaceuticals will receive a license for exclusive worldwide development, manufacturing and marketing rights to the novel BriLife coronavirus vaccine developed by the Defense Ministry’s Israel Institute for Biological Research (IIBR). BriLife is based on a previous, FDA-approved vaccine platform that was further optimized by IIBR and targeted towards Covid-19. Because it is a live-virus vaccine, NRx anticipates rapid and affordable industrial scaleup and manufacturing.

“As the first-generation Covid vaccines are increasingly challenged by rapid mutation of the coronavirus, we aim to develop a vaccine that can rapidly scale at low cost to serve the needs of both the developed and the developing world,” said Chaim Hurvitz, who is director of NRx, chairman of Israeli private equity group CH Health, former director of Teva Pharmaceuticals and former president of the Teva International Group.

Vials BriLife, the experimental Covid-19 vaccine from the Israel Institute for Biological Research. (Ministry of Defense Spokesperson’s Office)

Hurvitz is co-leading this initiative with NRx Pharmaceuticals chairman and CEO Dr. Jonathan Javitt, a public health expert who had leadership roles in seven successful healthcare IT and biopharma startups and led drug-development programs for Merck, Allergan, Pharmacia, Novartis and Pfizer.

Javitt tells ISRAEL21c that BriLife presents the entire spike protein of the coronavirus to the body’s immune system, while mRNA vaccines present a small slice of the spike protein to the immune system.

“We expect BriLife will create a broader immunological response and will enhance protection against Covid-19 and its variants,” says Javitt.

BriLife is continuing Phase II clinical trials in Israel and the nation of Georgia. Phase III trials are to take place in Georgia, Ukraine and other European countries.


MigVax, a vaccine-development startup spun out of the Israeli Science and Technology Ministry’s Migal Galilee Research Institute, is developing an oral Covid-19 vaccine, MigVax-101. This “sub-unit” vaccine contains pieces of coronavirus protein (not live or dead virus) delivered by mouth to stimulate antibodies and immune cells to fight coronavirus in mucosa, blood and cells.

On June 10, MigVax released results from preclinical tests on lab rats that demonstrated the potential effectiveness of MigVax-101 as an antibody booster for previously vaccinated people.

Now the company is raising funds to launch Phase I and Phase II human clinical trials. If such trials prove successful, the vaccine could be commercialized within a year after the trials begin.

An oral vaccine offers significant advantages over injected vaccines because it could be taken at home – no appointments, etc. Although it would have to be refrigerated, it would not need “deep freeze” conditions that make the mRNA vaccines expensive and difficult to ship and store.

MigVax says its vaccine candidate is uniquely positioned to tackle new variants because the subunit can be adapted quickly to novel variants. And its protein components are stable, meaning the vaccine may remain effective for longer periods before requiring a booster.

Furthermore, MigVax-101 could be more acceptable to a wider population, including people wary of receiving injections of genetic or viral material, as well as infants, children, pregnant women and others.

Commented Prof. Itamar Shalit, MigVax’s infectious disease exper: “Oral boosters such as our MigVax-101 will be key enablers that will help health organizations the world over transition from ‘panic mode’ to routine, due to their ability to reduce the cost and expand the reach of ongoing vaccination programs.”


Another oral Covid-19 vaccine is under development at Oravax Medical, a subsidiary of Jerusalem-based Oramed Pharmaceuticals formed last March as a joint venture with India-based Premas Biotech.

Oravax capitalizes on Oramed’s proprietary protein oral delivery (POD) technology and Premas’ exclusive virus-like particle vaccine technology, which will target three SARS CoV-2 virus surface proteins – including proteins less susceptible to mutation. That could make Oravax potentially effective against current and future mutations both as a standalone vaccine as well as a booster for previously vaccinated people.

“Our vaccine is a particularly strong candidate against the evolving Covid-19 virus due to its unique targeting of three proteins rather than one,” said Nadav Kidron, CEO of Oramed.

Oravax completed a successful pilot study on animals. Now the vaccine candidate is being tested in animals against variants including the Delta variant. Proof-of-concept clinical trials are soon to start in Israel at Tel Aviv Sourasky Medical Center to measure the level of antibodies and other immunity indicators.

Kidron has said that Oramed initially wants to target its vaccine to countries that haven’t been able to afford mRNA vaccines for their populations. An oral vaccine, as stated above, is less costly to ship, store and administer without the need of healthcare professionals.

Early stages

Several other potential Israeli vaccines are in early stages of development, some of them in labs at universities including the Technion-Israel Institute of Technology, Tel Aviv University and Bar-Ilan University.

An oral sub-unit coronavirus vaccine being developed in Rehovot at TransAlgae would use an edible delivery vehicle based on engineered algae. Bioencapsulated inside the algae, a specific coronavirus protein molecule travels intact through the digestive system to stimulate its target, the immune system.

Algae growing at TransAlgae in Rehovot. Photo: courtesy

Eyal Ronen, VP for business development, tells ISRAEL21c this vaccine candidate is undergoing preclinical trials. TransAlgae is seeking collaborations and strategic partnerships with American companies to advance development. The company’s main field of expertise is animal and fish vaccines as well as crop insecticides.

“We are not a pharma company and were not interested in going into human health at this moment. But our shareholders were asking us, why not use this for human beings? We took the challenge,” says Ronen. 

This article is reprinted from Israel21c.org.

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