Back to Basics; The Novavax Vaccine – Interview With Dr. Naor Bar Zeev

By Rafael Hoffman

After more than a year and a half of available COVID vaccines based on relatively new technology, the pharmaceutical company Novavax recently won CDC approval for distribution in the United States for its vaccine, based on more traditional immunization methods.

Its release comes as the omicron BA.5 COVID strain has swept the world, spreading a new wave of infections, driving high numbers of affected people, but remaining mild compared to earlier outbreaks.

To gain a clearer understanding of the Novavax vaccine and the new strain, Hamodia spoke with Dr. Naor bar Zeev, pediatric infectious disease physician and associate professor of vaccine sciences at the International Vaccine Access Center, Johns Hopkins University.

Please explain the difference between the Novavax vaccine and existing mRNA vaccines.

The Novavax vaccine is based on fundamental principles that have been in use for decades. The vaccine presents the immune system with a protein that is an exact copy of the spike protein on SARS-CoV-2, so that protective antibodies are formed by the body. In mRNA vaccines, the body’s cells produce the spike protein. In inactivated vaccines (not available in the U.S.), the virus is killed and then presented to the immune system. Here the mimic of the protein is presented on tiny particles.

The use of proteins in vaccines is very old. It’s what’s been used in the triple antigen DTP (diphtheria, pertussis and tetanus) shot for over half a century. Here the technology used to produce the proteins is new.

Does that mean that there is a lower risk level, since the technology has been in use for some time?

One should never take safety for granted and assume that there’s nothing to be worried about or even assume a lower level of risk. Safety needs to be positively demonstrated. It’s always on us to demonstrate safety, and just because the technology has been used broadly with different types of proteins that isn’t itself sufficient reassurance. You still need to go through the most rigorous testing and actually demonstrate safety. You can infer the presumption of safety from accumulated evidence over time, but that’s not direct proof of safety.

In that vein, a big advantage the mRNA vaccines have is that by now they’ve been used in billions of doses, so we now know their safety profile and their risk profile very well indeed.

The advantage, I would say, for protein vaccines as a class, not specifically the COVID vaccine, is that they’ve also been used for decades. But still, each time a new product is made, it has to go through safety testing.

What role do you think the Novavax vaccine will fill?

I think it will potentially be a useful booster for populations that have already been primed with other vaccines. It’s just an issue of when it came to market, and that’s the only real “market share” left, to use capitalistic terms. Of course, there is a significant population that has never been vaccinated, but it would be somewhat surprising if suddenly that remaining population decides to use Novavax just because the technology has been around longer. 

The U.S. population has not been very rapid in its uptake of boosters compared to Israel or some other countries. There has been some data out of Israel that third and fourth shots reduce mortality rates for the elderly and other high-risk people, so if Novavax becomes a good candidate for boosters, that could be useful. Their product is not yet licensed for children, but for now, that is not part of the Novavax discussion.

Are there any new risks or increased risk Novavax presents compared to RNA vaccines?

There have been reports of a small number of severe allergic reactions, which is expected with any new product. There are people in the world who are allergic to any range of things, which could include elements found in vaccines. People who know that they have any serious allergies should speak to their doctor about safe administration. Similar reports occurred with the introduction of Pfizer’s COVID-19 vaccine. Safety concerns are sometimes referred to as signals. These signals are then investigated further to see if they are real, if they are causally linked, how frequent they are and so on. As we saw with other COVID-19 vaccines, clinical trials alone can’t detect very rare events. These are found in safety surveillance after introduction. But by definition, these adverse events are very rare indeed. Every safety signal is investigated.

Do you think this vaccine will move the dial among the 1/3 of unvaccinated Americans?

People have had ample opportunity by now to get vaccinated, and people’s views are entrenched. The need for vaccination certainly still exists, and infection rates are climbing again, but the omicron subvariants are causing milder disease than was observed at the start of the pandemic. Of course, that could change again with a novel variant, and I hope that doesn’t happen.

Also, we now know more about the protection that past infection provides and even more so hybrid immunity which arises from infection and vaccination (in either order). We know that there is residual and fairly robust protection from severe disease and hospitalization, though this is improved with boosting vaccines. COVID-19 remains a nasty illness and is still dangerous for high risk groups. Infection provides subsequent protection that is true, but at the cost of risking serious illness in the first place. Vaccination is still the best option.

At the start of the pandemic, we had a wholly susceptible population and a nasty virus. Now we have largely an immune population (either from vaccine or from past infection) and a somewhat milder though highly transmissible disease. At this point, there are very few people getting it who have not been primed by infection, vaccination or both. There remains a real and measurable benefit of vaccination, but the absolute benefit is more modest than it was. Our job is to give an honest appraisal of the pros and cons, the benefits and risks, not to panic people into compliance and not to generate or repeat propaganda. In my view, we should respect people’s right to make their own informed decision about vaccination. That was and remains my view. This is especially true now that COVID-19 vaccines largely reduce disease but have a lesser impact on transmission than they did initially.

In general, as those vaccinated get further from their injections, does the need for boosters grow or are healthy people just as well getting exposed to variants as they emerge? Knowing what we do about the effectiveness of hybrid immunity, are vaccinated people better off without boosters?

The answer varies depending on whether you are talking about a high-risk or low-risk person. High-risk people still have a far higher chance of experiencing severe disease after two and even three shots, so it’s very beneficial for them to receive a fourth dose and further reduce their risk level, including reducing risk of death.

For a person at low risk, a booster will reduce the risk further, but the absolute magnitude of effect will be modest. Because the vaccines are so safe, there is little downside to receiving them, but there is not a strong, compelling reason to keep boosting people at low risk. This might change with novel variants, but I doubt it will change much. In terms of public policy, there are pragmatic limitations to never-ending boosting, and it’s not feasible.

Infection provides good protection, that is true, but I would certainly not encourage people to get themselves infected.

As vaccinations have proven effective in mitigating serious symptoms, but not transmission, what is the logic behind vaccine mandates and the like?

In my opinion, there is no justification for these mandates. Vaccines for COVID-19 were not designed to reduce transmission. Our hope was that they would reduce severe illness, and they did this brilliantly with the added bonus of reducing transmission of the Wuhan strain.

Unfortunately, the public health goal posts then shifted from flattening the disease curve to eradicating SARS-CoV-2. This was never realistic and, in my view, led to very stringent interventions that caused a lot of harm. Once we saw that transmission of novel variants was not reliably reduced by vaccination, the argument for mandating vaccination evaporated in my view (many excellent public health practitioners would disagree with me). Thankfully, vaccine effectiveness against severe disease remained even against novel variants, though waning was seen, and this reverses for a time with boosting.

Once it became apparent that vaccines would never get rid of SARS-CoV-2 transmission, there were two approaches. One called for more lockdowns and mandates, working with the Wuhan strain playbook, and the other that said the costs of that approach are too high on people’s lives and the benefits do not justify it. The second school also said that it was a time to be modest and admit that we can’t get rid of the virus, we should be glad that we have ways of keeping most people out of the hospital, and that we should get back to our regular lives.

How much is known about the Novavax vaccine’s effectiveness in minimizing symptoms from new variants? How flexible is it? By the time it is available in quantity, it is almost certain that a new variant will be in circulation.

This is a difficult problem facing all vaccine manufacturers now. As far as I know, there are no specific studies yet looking at clinical vaccine effectiveness against BA.5, but there is emerging information about neutralization antibodies against these novel subvariants. Based on what we know, we can expect Novavax or the mRNA vaccines to reduce risks of severe disease and death for these subvariants as well.

From a manufacturing point of view, it is tricky to plan for which strain to best target. It’s not so much a problem on the scientific side, because its relatively easy to adjust a vaccine to a viral mutation. But the logistics of mass production, global distribution and so on are challenging.

Work is ongoing on a pan-corona vaccine that targets all SARS-CoV-2 regardless of variant emergence, and also on nasal vaccines that may induce local immunity in the nasopharynx that might be important for transmission reduction.

Is there a way to know if omicron BA.5 itself is milder or if more mild cases are the result of a non-naïve population?

So far, it appears that BA.5 is similar to other omicron subvariants. Baruch Hashem, it’s not coming back as a terribly bad virus.

That said, the question is not easy to answer and two interconnected factors are at play here. Population immunity is now widespread, at least sufficient to reduce severe outcomes. This on its own reduces disease severity.

But secondly, as a result of that, the virus has a choice to make, so to speak. Viruses usually must choose between how infectious they are and how harmful they are. It’s a kind of evolutionary trade-off. Less severe viruses are selected out because people who have mild disease continue with their daily lives, which encourages spread. Sicker people stay at home. A kind of accommodation between virus and humans occurs to reach a biological equilibrium. It is common in biology that when a species enters a new environment, it diversifies (we call that radiation) until it reaches balance with its new environment. We humans are the new environment for this virus, and it is accommodating to us, and we to it.

The question for scientists to watch is whether on the molecular level viral transmissibility and viral severity are genetically linked. If there is a likelihood of it becoming more infectious and severe at the same time, that could be very concerning. I do not think it is very likely, especially with a large population that is vaccinated, so it is no cause for concern, but it is something that researchers should be vigilant about.

How protected are people who were infected during the initial outbreak from the current strains?

There really isn’t clear-cut data out there to answer that question. Based on what we know, I would guess that somebody who had the Wuhan strain and was never vaccinated would have some level of ongoing protection against severe disease due to T cell memory, but it would not be very robust and certainly would not protect much against infection or moderate symptoms.

If they were infected and subsequently vaccinated, even with only one dose, or they had Wuhan and then had, say, delta a year later, they’d have far more protection. Just like in learning, chazarah is important for the immune system, and the more times and more recently it’s seen a virus, the more effectively it can respond to it.

What is your view on efforts to encourage parents to vaccinate their children against COVID?

Overall, and baruch Hashem, COVID-19 is not a disease that has been dangerous for most children, but there is a small percentage that has suffered severe cases and there have been quite a number of child deaths in the United States, R”l. And although it is true that many of these cases had serious preexisting medical issues, each is still a preventable tragedy and an infinitely valuable individual child. There is evidence that vaccination reduces the risk of severe disease, including ICU admission for children and adolescents. There is also some evidence that vaccines also reduce the risk of Multisystem Inflammatory Syndrome in children.

If you have a child that’s vulnerable in some other way, such as having cystic fibrosis, a cardiac anomaly, or severe asthma, there is no question that you should vaccinate your child. 

If you have a healthy child, the risks of severe COVID-19 are very low, but the risk of Multisystem Inflammatory Syndrome, though uncommon, affects all children, not only high-risk children. Again, vaccines are very safe, and the rational thing to do is to vaccinate, because the benefits of vaccination outweigh its risks. That said, the benefits are modest, because severe disease is rare.

I think it’s a good idea to vaccinate children, but there’s no rush to do it. More than that, I certainly don’t think that schools should be restricting entry based on vaccination or that parents should be put under pressure to do so. It’s far more important to save more serious discussions on vaccinations for diseases like measles, whooping cough, polio, and so forth. It’s not worth alienating parents through enforcing COVID-19 vaccination only to have these parents disengage from the normal childhood vaccines that are so much more crucial for children than COVID-19 vaccination.

Most people that get COVID now are thankfully not experiencing severe illness. Before the pandemic, if someone felt unwell, they would go about their business to the extent that their bodies allowed them to, and were not particularly interested in knowing exactly what virus they had. Is it time to go back to that? Is there still justification for testing if you think you have COVID or isolation if you do?

There is formal guidance from the CDC, of course, which is best to follow. But a sensible approach, I think, is that people should adjust their behavior based on the risk level of those in their immediate circle. If you have people who are at high risk — elderly, recovering from cancer or have some other condition — then their families should be more cautious — test, isolate, mask, boost and so on. If you’re in an environment where nobody’s at immediate risk, I think you can be more relaxed.

Vaccination and boosting will provide individual protection against severe disease but won’t confer much reduction in transmission. Masks and distancing work best if everybody uses them simultaneously, but that can’t carry on forever. The virus is out there and will remain so. We as a community are largely vaccinated and thus protected from severe outcomes. Life should continue. COVID-19 is important, and we shouldn’t be complacent, but it’s not the only concern; life is bigger and should be lived. We have a lot to catch up on!

While not a COVID issue, one that is very connected to the vaccination issue is the recent polio case in Rockland County, N.Y. How concerned should the public be about this news?

I would defer to local public health authorities who are conducting a thorough investigation and will be providing accurate data. Though it is worth noting a few points. From the information available, the case was not imported; infection occurred here in the United States. Testing of waste sewage water has shown the presence of polio for some time.

Most people who are infected with polio have no symptoms, and some have mild flu-like symptoms. This asymptomatic transmission and the presence of the virus in sewage systems suggests the virus has been circulating for a period before this local acquisition case of paralysis occurred.

Spread of polio depends entirely on the proportion of the population that is susceptible. But since most people are vaccinated, the focus should be to encourage those who are not vaccinated or whose children are not vaccinated to reconsider their position and to avail themselves of vaccination against polio and other important diseases like measles.

The occurrence of a single case is a sign of wider undetected transmission and thus of deeper gaps in immunological protection at a community level, due to lower vaccine acceptance. These gaps apply also to other diseases like measles, as we saw in 2018. Hopefully, we can close those gaps by having people agree to be vaccinated, and of course we daven for a refuah sheleimah for the affected individual.

Rockland country is offering vaccine walk-in clinics, or people should speak to their doctors about vaccination.