Why your coronavirus vaccine will probably keep working

It’s a nightmare scenario: A coronavirus variant escapes science’s cleverly constructed defenses and returns to spreading unchecked, sending more than a year’s work to develop and administer billions of vaccine doses up in smoke. 

The most recent cause for alarm is the highly infectious Delta variant, first identified in India, which is pushing up case numbers again in countries like the U.K. and Portugal, prompting some EU countries to issue a new round of travel restrictions.

But for now, public health experts say, it’s not time to panic.

So far, most argue, the chances of a runaway coronavirus mutation dodging the protective effects of a vaccine — known as an escape variant — appear slim even though some variants might swerve around immune defenses slightly. The main driver for the most recent spike in infections in some countries is in fact not a vaccine failure or an especially dangerous variant. It’s the fact that they had populations that have been only partially or not at all vaccinated — while some governments rushed to relax lockdown restrictions before large majorities were fully jabbed.

That’s not to say that authorities should lower their guard. There’s some evidence that vaccines are less effective against the South African variant. And as long as the coronavirus is spreading in other places, like South Asia and South America, the risk of a further proliferation of variants is real. Some of those, known as variants of concern, appear to be more transmissible and have been linked to a higher chance of hospitalization, with the Delta variant as one example.

With so much of the world still not vaccinated, the opportunities for further mutation are a chief concern for David Heymann, professor of infectious disease epidemiology at the London School of Hygiene & Tropical Medicine and distinguished fellow at Chatham House.

Nonetheless, “we’re in good shape,” he said. “With influenza, we have to wait six months for a new vaccine” due to the time it takes to harvest the active substance from chicken embryos. By contrast, mRNA vaccines can be modified and produced in six weeks.

It’s in everyone’s interest to ensure people acquire “a high level of protection” from vaccines to avoid a worse-case scenario, he added, warning that “right now that’s not occurring.”

So far so good

With much of Europe and the U.S. jabbed, the real-world data so far suggest the antibody immunity given by vaccines appears to be holding up.

This finding is a relief to scientists who had worried about the risk that, in theory, the pressure created by the vaccine-induced antibody protection could encourage particular mutations that allow the virus to sidestep vaccines. If this process is repeated for a number of generations, a variant might emerge that could totally avoid vaccine-induced immunity. 

To be sure, certain mutations of the spike protein — the part of the virus that latches onto target cells — lower the ability of antibodies “to neutralize and stop the virus from infecting cells,” said Gary McLean, a professor in molecular immunology at the London Metropolitan University.

But he believes there’s only so much a typical virus can change.

“It’s going to hit a wall at some point,” McLean said, adding that the coronavirus “may almost already be there.”

In short, there’s a trade-off between how much the virus can change — and thereby “escape” a vaccine’s effect — and how effective it can be in continuing to spread, he explained. Because current vaccines target the spike protein of the coronavirus, this is where changes in the virus have to concentrate. If the virus changes too much, it can no longer properly infect cells. 

“There’s going to be a point where the virus can’t mutate anymore because it’s done all the mutating it can possibly do,” he said.

Andreas Radbruch, scientific director at the German Rheumatism Research Center and president of the European Federation of Immunological Societies, also believes it’s “extremely unlikely that there will be an escape from the vaccines.”

So far, Radbruch said, research suggests variants are concentrating mutations in just a few locations on the virus’ spike protein.   

So while variants may pose problems for individual monoclonal antibodies, it’s unlikely that one “would escape the current vaccines,” he explained. This is because the body produces thousands of different antibodies that target different parts of the spike protein.

In this sense, it was lucky that the coronavirus has been comparatively “conservative” so far, he said. Unlike the seasonal flu virus, it cannot “come up with completely new spike proteins that don’t have any similarity to the existing one.”

That said, this feature poses a problem in another respect, specifically for monoclonal antibodies — one of the most effective treatments for severe coronavirus infections — because some target these individual parts of the spike protein. In the U.S., a number of states have even paused distribution of Eli Lilly’s antibody treatment precisely for this reason. 

Original sin

Meanwhile, how long the immunity granted by existing vaccines lasts is still an open question.

While researchers are looking into modifying the shots to better respond to circulating variants, some say that second or third generation vaccines based on different variants of the virus may not elicit as strong an immune response as the first-generation jabs.

At issue is what some call the “original antigenic sin” — the immune system’s tendency to mount a stronger defense against the first version of the antigen it encounters — either through natural infection or vaccination. This reaction, in turn, knocks out the immune system’s ability to mount as strong a defense against mutated forms of that antigen. This phenomenon has been seen with the seasonal flu and the ongoing problem that flu jabs — which are less effective than COVID-19 vaccines — need to be modified annually.

“When you get reinfected with a new strain, your antibodies are more likely to be re-stimulated, to be provoked again to make more antibodies against the parts of the protein that haven’t changed,” explained Charles Bangham, professor of  Immunology at Imperial College London. 

So the immune system mounts a strong response to the bits of the antigen it recognizes, overshadowing the slower and weaker response to the mutated bits of the antigen it hasn’t encountered before.

However, Bangham isn’t concerned for now and sees this scenario more as a “theoretical danger.”

He notes that antibodies can recognize many parts of the spike protein that haven’t mutated and therefore still can be effective. 

Moreover, it’s not only antibodies that are primed; T cells also play an important role in fighting infections. “They recognize a lot of other parts of the spike protein,” said Bangham. If someone is naturally infected with Delta, they will also respond to other proteins in the virus, which tend to mutate less than the spike protein. 

“So both antibodies and T cells are still active against not only the spike protein but all the other proteins in the virus,” he said.

In Bangham’s view, the best way to avoid escape variants and mount a strong immune response to the evolving virus would be to design a “polyvalent” vaccine that contains parts of the Delta variant as well as Alpha and Beta (first identified in the U.K., and South Africa, respectively). “That is likely to cover a very high proportion of the infections” today and in the future, he said.

England’s Chief Medical Officer Chris Whitty agrees, noting that polyvalent vaccines “will hold the line to a very large degree against even new variants” within five years.

A fine line

For all the advances in science, policymakers must now grapple with the complexities of a partially vaccinated world.

In the U.K., for example, after an initial sharp drop in new cases, infections have started to increase rapidly again. The good news is that unlike during previous waves of the virus, mortality appears to be barely budging, even taking into account the lag between infections and deaths. Ministers decided in June to delay a full reopening of the country, but on Monday Prime Minister Boris Johnson announced plans to drop final restrictions on July 19, including mask wearing, and urged the public to use their own “judgement.”

Meanwhile, other countries with relatively high vaccination rates are facing new challenges. Some, like Poland and Romania, are dealing with a high degree of vaccine skepticism. And even within the ranks of people who have received a shot, some are immunocompromised or suffer from existing conditions like diabetes that make them more vulnerable.

Danny Altmann, professor of immunology at Imperial College London, sees this shift as moving away from “black and white debates” during the height of the pandemic when thousands were dying daily. Now, policymakers have to take a more granular and nuanced view, particularly when it comes to deciding the right level of protection to minimize avoidable deaths in vulnerable populations.

“The more variants that come around the bend, the more evasive they are, the more problems we might have with … people who don’t have good enough immunity,” he explained. “The question then becomes: What’s my tipping point when it becomes unacceptable, where I either need a vaccination program with a modified vaccine, or I need more frequent boosters.”

“The debates are much more complex,” he added. “But I don’t think that I’m going to have the same conversation with you in a year’s time saying ‘My god, that Zeta variant took us by storm and conquered the world.'”

This article is part of POLITICO’s premium policy service: Pro Health Care. From drug pricing, EMA, vaccines, pharma and more, our specialized journalists keep you on top of the topics driving the health care policy agenda. Email [email protected] for a complimentary trial.