NEW YORK — The world is waiting for a new generation of COVID-19 vaccines that last longer and can actually prevent infections.
The existing shots have averted millions of deaths and hospitalizations, but the public’s willingness to get vaccinated seems to shrink with each new round of boosters. A new approach is needed to withstand the waves of variants.
I asked Peter Marks, the director of the Food and Drug Administration’s Center for Biologics Evaluation and Research, to explain what’s ahead with the next vaccines. Here is an edited transcript of our conversation:
Lisa Jarvis: In the early months of the pandemic, mRNA vaccines from Moderna and Pfizer/BioNtech and adenovirus vector vaccines such as J&J and AstraZeneca’s were the fastest route to getting shots in arms — and, happily, they worked. But the virus keeps evolving, and the efficacy of these shots wanes a little more quickly than we’d like. How urgent is the need to evolve our vaccines?
Peter Marks: The good news is we have a generation of vaccines that can be deployed in a way that they can keep us protected against severe disease. With appropriate boosting, we will be able to protect the population from the worst outcomes from COVID-19.
The challenge is, not everyone wants to get vaccinated all the time. And then from the standpoint of productivity, you don’t want a vaccine that just prevents severe disease. You’d like to have people not having to stay home for days from work.
We need a vaccine that helps prevent disease entirely. It’s not the same emergency that we had back in 2020. But I feel an urgency to this. We need vaccines that will give us mucosal immunity. In other words, get the virus where it starts, in order to interrupt the constant cycle of transmission.
You’d like something like a nose drop. You prevent not only severe disease but also transmission. Something like that would be a dream, because it would also be possible to use in low- and middle-income countries, which is really critical here. If we don’t stop the cycle of replication, this virus is probably going to give us new variants that will ultimately overcome our current countermeasures.
LJ: How hard it will be to test the future generations of vaccines?
PM: I don’t think we’re going to be able to test these vaccines on people who have not been exposed to COVID, because we’re not going to find them. You’ve either been vaccinated or you’ve probably been naturally exposed. We will have to test new vaccines in the setting of pre-existing background. But that can be done. We have the technology to look at T-cell responses, we have the technology to look at antibody responses to a specific vaccine. We’ll probably have to do this largely on immunologic criteria, at least initially.
The other way would be if we are unlucky enough to get a variant that completely escapes the current vaccines. Then you’re back in the setting of being able to do a clinical trial of a new vaccine. Honestly, if there’s one thing I have learned during the pandemic, it’s a healthy respect that we have a very formidable adversary and that we’re very often wrong. We have to be nimble.
LJ: Some immunologists and virologists have called for the FDA to look beyond neutralizing-antibody levels when assessing COVID vaccine responses. Should the agency be asking for more comprehensive data on immune response to current and future vaccines — for example, asking companies to measure memory T-cells?
PM: I do think that we need to look more robustly at the totality of the immune response here, not just antibodies.
We don’t have a perfect correlate of protection yet. We’re using antibody levels because it is a good first approximation, but that doesn’t really help us understand the durability of response, the strength of response. We don’t know exactly that panel of tests that we need. It’s something we’re working towards with our partners, including NIH and partners in industry.
LJ: The FDA’s early playbook for responding to SARS-CoV-2 grew out of its experience with Ebola, Zika and the original SARS. Those were all relatively acute emergencies. We’re into year three of this pandemic. Are there things you need to adjust about your regulatory strategy?
PM: When we started out, there was the hope that this was going to be a one and done. We would get enough people vaccinated and this thing would eventually just go away. Then we realized we needed the boosters. Now we realize we have something that looks somewhat like influenza in that it looks like it could become an endemic virus that comes around every year. That does shift the playbook to more of a long-haul strategy. We have to start thinking about vaccines that we can adjust strains of once a year and make it more of a flu model rather than saying, OK, every five months or four months, you’ll get another booster.
The idea here is that next year we have one campaign, and we don’t have to follow it up with another booster campaign. Ultimately, next-generation vaccines would ideally help hold us for that full year.
LJ: That’s helpful because I hear from many people who were very eager to get the first round of shots, and maybe even their first booster, and they are starting to have vaccine fatigue. When will we get to a point where the public feels as if they understand the schedule?
PM: This is going to be what I would consider a transitional year. The hypothesis now is that this is going to look somewhat like influenza. In this 2022-23 season, instead of just getting vaccinated against influenza, you’ll also get your booster for COVID-19. And we’ll see how that goes.
If people who get that boost do well and we seem to have avoided another big wave from October to March-April of next year, we will have gotten people used to that.
LJ: Is there anything you’d like to communicate to people who are hesitant to get their next booster or are confused about when to get their next booster?
PM: No. 1, the vaccines definitely work. No. 2, everyone age 5 and up should have their third dose at the appropriate time. It’s clear that boosters not only work but they work well at helping to reduce the risk of serious disease including hospitalization and death. People who are 50 and up really should consider that fourth dose because the data from Israel are quite compelling that it reduces your risk of death for very, very few side effects.
I would leave you with the fact that if you get boosted now, it’s not going to preclude your getting an updated booster in the fall. If you haven’t had COVID, you should at this point have either three or four boosts, depending on whether you are less than 50 or over 50.
Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, health care and the pharmaceutical industry. © 2022 Bloomberg Opinion.