Boosters, Vaccines for Children, and the Future: Deepta Bhattacharya Tells Us What to Expect Next From the Pandemic

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As the delta variant continues to spread rapidly and vaccine boosters begin, many obstacles remain before us in the COVID-19 pandemic. Expert immunologist and NYSCF — Robertson Stem Cell Investigator Alumnus Deepta Bhattacharya, PhD (University of Arizona) recently joined NYSCF CEO & Founder Susan L. Solomon, JD, for a fireside conversation about virus variants, vaccine boosters, and immunity. 

What is the current status of the pandemic?

“What we’re going to be looking at for a little while is basically these spikes and these valleys [of infections], but what should happen is that the magnitude of those spikes should start to decrease as people get immunity one way or the other – obviously the preferred way is to get it through vaccination,” explained Dr. Bhattacharya.

“What will also happen is that the delta variant is going to find people who don’t have immunity yet. And I think we’ve probably heard and seen some of these headlines from The New York Times saying that herd immunity is impossible. What that basically means is that Delta will find a way to you if you don’t have immunity. There’s no indirect protection.”

“Delta came and I think many of us who work on virology and immunology were really taken aback at just how transmissible it was. However, it will come to an end, or at least certainly won’t be in this form for that much longer.”

Should we be worried about new variants?

Dr. Bhattacharya stressed that the major challenge right now is how transmissible the virus is, or may become in future.

“I think we’re still in a place where the most problematic property of the virus is how transmissible it is or it isn’t,” he remarked. “The original versions of COVID – the ‘COVID classic’ I’ll call it – had a certain degree of transmissibility. And then there’ve been subsequent variants that have emerged since then that are two or three more times transmissible. And that’s where we’re at right now with Delta, which is why it has been difficult to keep it under control.”

“This is a virus: there will be new variants. It will change. But what we really want to do is get to a point where we force the virus to make a choice: either make a bunch of copies of itself really quickly and be really transmissible, or evade the immune system and take a fitness cost,” he said. “We’ve seen that a couple of times – there have been mutations that looked like they were going to be a problem for immune escape and ended up not being so because the virus petered out. So, I think we just need to wait and see what comes next. I don’t anticipate a complete loss of immunity anytime soon.”

How strong is the immunity we gain from the vaccines?

Last time we talked, we had just gotten some of the data from Pfizer and from Moderna, and both of them were remarkably effective (around 95%) against COVID classic,” Dr. Bhattacharya recalled. “Right now, we’re a little lower than that. And there’s a couple of reasons for that.”

“In my opinion, if you really look at the data, I think the most important factor here is Delta. And it’s not really about immune escape, but rather that when someone gets infected with the Delta variant, it replicates so quickly and it generates so many more copies of itself that when someone who has it breathes or coughs, you’re just exposed to a ton more virus than you were before. What that then means is that you must have more pre-existing antibodies to protect against it.”

“However, the most important thing is that the immunity you get from the vaccines can keep you out of the hospital and keep you from dying from the infection, and in that regard, unless you have some preexisting condition, the vaccines are actually holding pretty steady. They do a good job at this.”

How do antibody levels look after vaccination?

“Antibodies decline. But, that’s a normal part of the immune response,” noted Dr. Bhattacharya. “Basically what happens is that after you get infected or vaccinated, you generate this huge amount of antibodies early in the response, but the antibodies that are being made early aren’t that great. They don’t stick that well. The analogy that I’ve used is that it’s sort of like a stamp before it has been licked. “

“Then what happens is there’s this intense competition process, the weaker antibodies are kicked out, and the cells that produce them die off. And then you sort of expand out the best antibody-producing cells, and those are the ones that persist. So you just don’t need nearly as many antibodies to protect you later in the response as you do early on.”

How well do booster shots work?

“We have some really remarkable data from Pfizer that followed the original trial participants and gave some of them a third shot and look to see how much better those people who got boosted are doing compared to those who got just two shots,” said Dr. Bhattacharya.

“What they found is that there’s a 20 times lower risk of getting symptomatic infection at all [if you get a booster]. The likelihood of passing it on to someone else is much less if you have a booster because the likelihood of getting infected in the first place is so much lower.”

“However, I would say that the most important shots we can give right now are to people who haven’t had any doses yet.”

If you’ve already had COVID and recovered, do you need a second shot? Do you need a booster?

“If you look at antibodies and T-cells, there’s no additional benefit from that second shot afterwards [for those who have already recovered from COVID-19],” explained Dr. Bhattacharya. “Actually, if you look at the immune response after one shot in someone who has recovered from COVID, it’s better than someone who’s gotten just two shots of the vaccine. It’s what we call hybrid immunity.”

“So, if I were in that position and had covered from COVID, I would stop after one additional shot.”

If you received a Johnson & Johnson vaccine – should you get another dose of it, or should you get an mRNA vaccine as your second dose?

“If you look at the antibody levels in someone who had a J&J vaccine and then an mRNA vaccine [Pfizer or Moderna], they’re way higher than someone who gets two shots of J&J,” remarked Dr. Bhattacharya.

Dr. Bhattacharya in the lab

“J&J is an adenovirus vaccine [a vaccine containing a virus that has been altered so it can’t make you sick]. And so what can happen in these kinds of vaccines is that you generate immunity not only to the spike protein, but also to the adenovirus itself. So that when you come back with another adenovirus immunization later on, you’ve got a bunch of antibodies that prevent that adenovirus from doing what it needs to do. If I were in that position and I had received the J&J shot, I’d get an mRNA shot as my second dose.”

If you had a breakthrough infection, do you need a booster?

Dr. Bhattacharya thinks no.

“There’s nice data that came out of Dan Barouch’s group just a couple of weeks ago where they followed people from the big Provincetown outbreak where the overwhelming majority of people were already vaccinated,” he said. “They’ve now gone in and looked at some of the antibody levels, and it’s sort of like what it is when you get infected and then a booster – there’s an astronomical antibody response.”

“You have so many antibodies that are already there that even if you get another vaccine, those antibodies just suck up whatever bit of spike protein is made, and then you don’t really generate much of a new immune response,” he added. “That’s again, one of the reasons why, when you’re really maxed out, I don’t see the point of just rigidly holding to this regimen where you’ve got to get two shots, or you’ve got to get a booster. I think we need to be a little nimbler and more logical on this.”

When will we hear about vaccinations for children under 5 years old?

“I’ve heard from governmental officials that they anticipated that the youngest kids are a few months behind the five- to 11-year-olds,” said Dr. Bhattacharya. “So, my guess is it’ll probably be sometime early next year.”

“I think this is one of the challenges we have: the relative likelihood of a young child getting extremely sick is low, but at the same time, I think we must recognize what that would mean. Even if it’s rare for a young child to get COVID and have severe consequences, it’s still a preventable issue, and not attending to it is unacceptable.”

How can we make antibody testing more useful?

“I think what we need to do is to start to move towards antibody tests that actually measure antibody function, not just quantity, because what you really want to do is measure the ability of antibodies to block the virus from getting inside of cells,” noted Dr. Bhattacharya.

“The ultimate goal is that you take a test and that will tell you if you need a booster or not. You don’t want to have to go through another five-month-long clinical trial every single time you want to assess whether a booster is necessary – you need an immune correlate. And I think we’ll get there. It’s just been hard because what we needed before Delta is different than what we need now.”

Will we need to get COVID booster shots every year like we do for the flu?

“I think there’ll be options to take a booster annually – whether you need to take it annually is a different thing altogether,” Dr. Bhattacharya said. 

“There’s a lot of differences in the biology of coronaviruses and flu viruses. The flu virus can actually undergo pretty dramatic changes: if you get two different flu strains that infect the same cell, they can swap pieces around and you basically are left with something completely different than what went in. The coronaviruses by and large don’t do this. They sort of just slowly mutate one thing at a time, so I don’t anticipate the same level of viral evolution in coronavirus as we do for flu. But my guess is that [boosters] will be made available to whoever wants it every year.”

What is the latest on COVID-19 treatments, like antivirals and monoclonal antibodies?

“There’s two different categories of drugs. There’s the oral antivirals (Merck has one I imagine will be authorized very soon) and then Pfizer has another one,” explained Dr. Bhattacharya. “The mechanism of action is different for those two, and so I can envision a strategy where you use both to sort of shut off viral infections really quickly.”

Dr. Bhattacharya believes having better options for mitigating the disease after infection will be important for navigating the future.

“I think it’s important to make it clear to people that there are options so that even if you do get a breakthrough infection, there are things we can do to shut things off and make sure that it doesn’t go that badly. I mean, hopefully that’s a really important step towards returning to normalcy.”

“The monoclonal antibodies are a little different because they, for the most part up until this point, have been used after you have symptoms, which is not the ideal time to use them. What ideally you want is those antibodies to be there ahead of time. AstraZeneca now has a new monoclonal antibody out that just looks incredible. They’ve engineered the stem of the antibody so that they stick around for very long periods of time.”

“If it’s something that you need once a year, then that’s not that much different than the vaccines, and I think it’s a totally viable option. So it’ll be interesting to see if people who are reluctant to take the vaccine might be amenable to taking monoclonal antibodies.”

When will things get back to normal?

For those visiting family over the holidays, Dr. Bhattacharya stressed that there are multiple options for protecting oneself, but the most effective measure by far is vaccination.

“There’s a lot of ways in which you can protect yourself, and some may be more palatable than others to people in your group. Vaccination is better than anything else, but there are other things that you can layer on. As we talked about, there’s rapid tests. I can’t imagine that people are going to want to mask around their families indoors, but it’s theoretically possible.”

“There certainly are cases where fully vaccinated people transmit to each other, but the likelihood of that happening is so much less than if you have an unvaccinated person in your group. I can’t emphasize enough [that vaccination] is the path back to normal.”

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