Vaccines, Variants, and Immunity: Deepta Bhattacharya Answers Your Questions About COVID-19

Watch the Fireside Chat video and read the summary below.

We are in something of a race between COVID-19 vaccines and emerging virus variants, and many questions still remain about what these variants will mean for vaccine efficacy and when we will return to normality. NYSCF – Robertson Stem Cell Investigator Alumnus Deepta Bhattacharya, PhD, an immunologist at the University of Arizona who studies antibody responses to vaccines and infections, recently  joined NYSCF CEO & Founder Susan L. Solomon, JD, for a fireside conversation to talk about all things COVID-19 vaccines, variants, and immunity. 

How well are vaccines working against preventing COVID-19, hospitalizations, and death? 

Dr. Bhattacharya stressed that the Pfizer/BioNTech and Moderna vaccines are showing exceptional efficacy in preventing symptomatic COVID-19.

“[Both vaccines] reported efficacies of about 95% for preventing symptomatic disease relative to the unvaccinated placebo cohort, which is pretty remarkable,” he noted. “There’s about a 20-fold reduced risk of getting COVID-19 relative to someone who’s in the unvaccinated group. 94-95% efficacy is right up there with the best vaccines we’ve ever seen. This is as good as it gets.”

This data suggests that the vaccines are also effective at preventing severe COVID-19.

“I think what we need to do is rely on what we understand about basic immunology, which is that the hardest thing in the world for a vaccine to do is to prevent infections. The next hardest thing is preventing any symptomatic disease, and that’s what the primary endpoints [of the clinical trials] were designed for,” Dr. Bhattacharya explained. “ I think there’s every reason to expect that severe disease efficacy is going to be better than the overall efficacy for preventing any symptoms. So, if it’s 94-95% at preventing symptomatic disease, I think we can expect that it’s going to be better than that for severe disease.”

Johnson & Johnson’s vaccine was the only clinical trial to assess hospitalizations, which appear to also be reduced for all the vaccines.

“The Johnson and Johnson trial was the only one that explicitly looked for prevention of hospitalization as a primary endpoint,” said Dr. Bhattacharya. “For the other vaccines, so few people got hospitalized, even in the placebo group, that the overall effect is a little bit hard to quantify.”

There have been no reported deaths from COVID-19 following vaccination for any of Pfizer/BioNTech, Moderna, or Johnson & Johnson’s clinical trials.

“No one in the trials has died from a breakthrough infection yet,” he continued, “When you’re talking about hundreds of millions of people, we’ll probably hear some things, but I think the likelihood [of death from COVID-19 in a fully vaccinated individual] is very low.”

“I still am uncertain whether or not [the Astrazeneca vaccine] will ever get an Emergency Use Authorization here or not,” said Dr. Bhattacharya. “There were some problems with the trials, as we talked about. It sounded like we were probably ready to overlook those things because there’s been a US-run trial. Even with these somewhat unwarranted worries about blood clots, I’m not sure AstraZeneca will take off here.”

What is a variant and how do they arise? Are the variants more contagious and/or lethal? 

Like all viruses, SARS-CoV-2 is constantly mutating to form new variants, but Dr. Bhattacharya stressed that most of these mutations are harmless.

“One of the best pieces of advice I got from one of my viral evolution colleagues is that a variant is innocent until proven guilty,” he remarked. “I think one of the things we need to recognize is that this is an RNA virus. It will undergo mutations from the ancestral strains, and the overwhelming majority of those changes are neutral or detrimental to the virus. They’re not things we need to worry about.”

In fact, the SARS-CoV-2 virus did not seem to produce more dangerous variants until the B.1.1.7 strain emerged in the United Kingdom.

“I would say up until about November-ish of last year, it really just seemed like the genetic diversity of this virus is quite low, and what changes were happening were neutral or inconsequential at best,” recalled Dr. Bhattacharya. “I think that the major one started worrying people was the B.1.1.7 variant. I still think that is by far the most problematic one, because there’s really no question at this point that it is more transmissible, and the evidence is really overwhelming for that. Every place has been introduced and eventually takes over. But the good part about that variant is that we’ve seen from data in Israel that it is fully susceptible to vaccination.”

While the B.1.1.7 strain is more transmissible, this fortunately doesn’t mean that it has gotten better at evading the immune system, as there aren’t enough immune people out there to sufficiently challenge the virus.

“Once you actually start getting some immunity within the population, then [the virus can’t just] bounce from one person to another – it has to evade the immune response to productively infect.” explained Dr. Bhattacharya. “Right now, we’re nowhere near the herd immunity threshold, so if a variant is more transmissible, it’s not because it’s evading the immune system.”

Dr. Bhattacharya also explained that the variants that popped up last winter were likely due to the widespread nature of the virus.

“Where we really ran into trouble was that there were so many worldwide infections that there were so many possibilities for a variant to emerge and get selected out. There’s a nice article in The New York Times that explains how B.1.1.7 probably emerged in an immunocompromised individual. So you can have these rare events that take off. If we get a lot of people vaccinated, and a lot of people already have natural immunity, then those case counts are going to drop, and there’s fewer opportunities for these rare jackpot mutations like B.1.1.7 to emerge.” 

Do the vaccines prevent people from transmitting the virus?

“One of the concerns had been that the vaccines might be reducing symptoms, but not actually reducing the infections,” noted Dr. Bhattacharya. “So what would that mean? If we’re reducing 95% of symptomatic disease, is that then being counterbalanced by a 95% increase in asymptomatic disease? That’s what it would have to be if there was no impact on infections, but in fact, it’s also reducing overall asymptomatic infections as well.”

Even if you do happen to contract a rare breakthrough infection, it appears that transmitting the virus after receiving the vaccine is still far less likely.

“What we’re also now starting to see is in people who do get breakthrough infections, that the overall viral load [the amount of the virus in your body] is down by somewhere between 4- to 16-fold,” said Dr. Bhattacharya. “It’s not much of a stretch to think that if you are unfortunate enough to get a breakthrough infection, you will be far less likely to transmit to someone else.”

Where do things stand on vaccinations for children?

Dr. Bhattacharya stressed that even though children are less likely to transmit the virus, vaccinating them will still be important for reaching herd immunity: when enough people are immune to curb the virus from mutating and finding new hosts to infect.

“We’re talking about trying to achieve herd immunity and that’s not an easy ask if we have a good 20% of the population that is not vaccinated,” he noted.” We know that kids are less likely to transmit, but less likely to transmit doesn’t mean impossible.”

If community transmission is largely reduced by vaccination of adults, then Dr. Bhattacharya thinks we can delay vaccination of children, but reaching this low level of transmission will be challenging.

“A lot of our behavior is going to be driven by community transmission, and the vaccines are certainly going to help with that. And if it drives it down to the point where there’s less than one case for a hundred thousand, then I think we can afford to wait a little bit on terms of vaccinating children, but if we don’t hit that, then obviously [vaccinating children] is something we need to factor in.”

How long do immunity from natural infection and immunity from vaccination last?

Vaccines appear to confer strong immunity, but it is still unclear how long the immunity lasts.

“There are two factors that control how long you’re immune for: one is how long do the immune cells and antibodies persist, and the second is whether the virus changes or adapts to evade what’s already there,” said Dr. Bhattacharya. “Frequency of reinfection after vaccination is very low, and the antibodies, as far as we can tell, seem to be maintained reasonably well. Will that last for another year, another 10 years, or another 20 years? We don’t know that. We don’t have a lot of long-term data. These are the first times that we’ve really seen the mRNA vaccines roll out. Moderna has published [a paper] in the New England Journal of Medicine showing data out to about four months that looked really good to me.”

For natural infections, antibody levels are far more variable, but re-infections are still low.

“The level of immunity and antibodies after natural infection is extremely variable. And yet when you look across the frequency of reinfection, it is very low. It’s not zero, but it’s very low,” explained Dr. Bhattacharya. “So that to me says that it doesn’t take very much to protect [from infection]. So that’s a very good thing because after that second dose, you’re so far above what we think is the protective level [of antibodies], that I think it is going to take a long time to get down below the level where you would no longer be protected.”

At the moment, it remains unclear whether booster shots will be needed down the line.

“Is this going to be something that ends up being more like polio or measles where you can basically drive the endemicity down to very low levels where it’s less of an issue, or is it going to be something more like the flu where we’re probably looking at annual vaccinations?” Dr. Bhattacharya asked. “I would say that there’s lots of predictions, but I think that anyone who boldly asserts that they know exactly how this is going to go is probably someone you shouldn’t listen to.”

Is it true that you get all your immunity in the first shot and the second dose is just to secure your immunity?

“I’m not sure that that’s quite true,” said Dr. Bhattacharya. “We see some pretty good responses after that first shot, but a huge amount of variability too – it’s almost like natural infection. Most people have pretty good antibody levels, pretty good T-cell levels [following the first dose], but then you have some people with really poor levels. The other advantage of getting that booster is it cleans up that variability and gets the set point a little bit higher.”

If you already had COVID-19, should you still get the vaccine?

“In some ways it’s a little bit hard to compare natural immunity to vaccine immunity because when you get infected, you’re getting infected in your nose or in your throat,” said Dr. Bhattacharya. “When you look at just the antibodies in your blood after natural infection, and you compare that to the vaccines, the vaccines do better unequivocally. But what the natural infections also do is they give you some local immunity at the site. If you look at the levels of reinfection in people who have recovered from COVID-19 and you compare that to the breakthrough rate of infections post vaccines, it’s about the same.” 

“I’ve been advising people that there’s certainly an advantage to getting a booster shot after you’ve recovered from COVID-19,” he continued. “But when we’re in a situation where the demand far exceeds the supply, you may want to think about waiting a little bit, because there’s no question that you’re a lower risk than someone who’s never seen it in the first place. I would definitely recommend people get at least one shot.”

Some studies have also suggested that people who have already had COVID-19 do not need to get the second dose. Dr. Bhattacharya suspects that this is probably true, but that there is no disadvantage to receiving both doses.

“It’s pretty consistent with what we understand about immunology. You form a bunch of memory cells after the natural infection and if they see something they recognize again, then they go nuts and trigger an immune response. So yes, I think that probably is true, and when we’re talking about dose sparing strategies and things like that to make sure that we get as many people immune as possible, as fast as possible, then I think that’s a perfectly reasonable direction to go. However, there is no downside to receiving a second dose.”

Do you think there will be enough supply for anybody who wants a vaccine to sign up for one in May?

“I don’t know,” admitted Dr. Bhattacharya. “I think that at the production levels for Pfizer and Moderna right now could use a little help, we’ll say. And then it gets into the questions of Johnson & Johnson. What I really hope is that they get Novavax online too. I hope that the FDA is willing to take the data from other countries because the Novavax trial was run very well. We have a hundred million doses that we’ve already purchased from Novavax. If we add up these four different vaccines, then I do think [we will have enough by May]. But it all falls to the FDA deciding whether or not they’re willing to take data from other countries and add Novavax to the mix.”

Dr. Bhattacharya also pointed out that America should also be planning how to aid in vaccine distribution worldwide.

“I’ve always been an advocate of thinking about this as a global pandemic. It doesn’t make sense for us to have 700 million doses. I really do think that we need to think about some of these underdeveloped countries and make sure that they get their chance too. There’s lots of people getting sick and dying in those countries as well.”

People are being encouraged to get whatever vaccine is available to them – do you agree with that?

“I’ve been a little bit uncomfortable with that messaging, to be honest, because we need to make sure that we’re getting these out to communities that have been hit especially hard,” noted Dr. Bhattacharya. “Here in Arizona it’s the Native American population. We know that Black and Hispanic communities have been just absolutely hammered by the virus. And I think that honest and open communication is really important as we try to get some of these vaccines out to these communities. When you see a headline of saying 95% efficacy, and then J&J reporting 66% efficacy, and insist that they’re the same, I just think that breeds a certain degree of mistrust.”

“Here’s what I would say: the choice before us at this point is vaccine or no vaccine. If the vaccine is J&J, that’s an awful lot better than no vaccine. I can also tell you anecdotally that in some of our own studies, we’ve seen people that have gotten the J & J vaccine, and then the first shot of Moderna and their antibodies go absolutely through the roof,” he continued. “So, I want to make clear that this is not a lifelong commitment. It’s not a marriage. If you get the J&J vaccine, you’re not stuck with that forever. It buys you some time and some protection, and it may be good enough. And if community transmission comes down by us all doing our part in getting vaccinated, then maybe the next booster is unnecessary.”

Do you think there will be another surge in infections this fall/winter?

“No, I don’t,” said Dr. Bhattacharya. “It doesn’t seem like it takes [many antibodies] to protect, so that’s a good thing. There are also many different places on the famed spike protein of the coronavirus [the protein that helps the virus bind to cells and initiate infection] where an antibody can bind and prevent or limit infection. The coronavirus, unlike the flu virus, has to sequentially mutate to get out of the way of antibodies [which will likely take a while].”

“So for fall and winter, my best guess is that no, [there won’t be a big surge], but three or four years from now, might we need some boosters? Maybe, in case there is a variant that proves really problematic.”

If you don’t have a reaction to the vaccine, does that mean it isn’t working as well as in someone who does have a reaction?

Scientists do not know whether a stronger reaction to the vaccine means better efficacy, but Dr. Bhattacharya suspects that if it does, then the difference isn’t that significant.

“The question is, do we really know that? We’re actually doing some of those studies right now. We have a huge antibody study that we’re running out of the University of Arizona where we’ve added questions [addressing this topic]. If you look at the trial data, some 75% of people will have some sort of reaction and presumably 25% or so don’t,” said Dr. Bhattacharya. “The question is whether it’s exactly the same, between someone who has fewer symptoms and someone who doesn’t. Frankly, we don’t know the answer to that, but I doubt it’s going to be a dramatic difference.”

Are we in a new golden age of vaccines?

With the world’s focus on an infectious disease and exciting new vaccines fueled by mRNA technology, Dr. Bhattacharya hopes that the future of all vaccines will be brighter following the pandemic.

“I think that we’ve long neglected infectious disease as a driver of human suffering,” he said. “I think in large part that’s because it is not as much of a burden in the more developed countries as other types of diseases, but it’s still the leading killer in underdeveloped countries. I really hope this pandemic does bring new attention to vaccine development and paying more attention to newly emerging pathogens that we really need to be getting a handle on and dealing with rapidly.”