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Commentary: Better COVID-19 booster vaccines are needed if we want people to take them

PROVIDENCE, Rhode Island: The public’s waning concern over COVID-19 is the main reason cited for plunging stock prices and impending layoffs at Pfizer. The company bet big that people would sign up for annual COVID-19 mRNA boosters the way they do for flu shots.

But people aren’t: On Dec 15, the United States Centers for Disease Control and Prevention (CDC) reported that only 18 per cent of adults had taken the latest COVID-19 shot, compared with 42 per cent who’d had a flu shot.

One challenge facing the fall booster campaign is the lack of a seasonal pattern for COVID-19. With the flu, there’s a predictable seasonal pattern and getting a shot in the fall can protect the vulnerable through the worst of the winter wave. By contrast, COVID-19 continues to show surges of activity all year.

But the bigger problem is the quality of the new COVID-19 boosters.

TEMPORARY INCREASES IN PROTECTION

Past boosters have offered weak, fast-waning protection against infection. And there’s little evidence that they prevent transmission.

The CDC is still arguing that they prevent spread of the virus, but some respected infectious disease experts call this incorrect. Some experts also argue there’s no evidence that giving young people multiple boosters does anything to lower their odds of infecting grandma or grandpa.  

There is a consensus that booster shots offer temporary increases in protection against severe disease and death, making them important for the elderly and people with certain health conditions. But there’s room to do better – maybe with a new kind of shot, or maybe with a smarter use of the many kinds of vaccines available today. 

At this point, it’s clear from all the infections that the vaccine isn’t living up to early hopes. “The initial impression that these vaccines were 95 per cent effective against symptomatic infection and 100 per cent effective against severe disease are no longer accurate,” said Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School.

That’s because our antibodies wane over time and the virus mutated much faster and more radically than scientists had expected.

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The good news is that those initial vaccines do continue to protect people to some extent from severe disease and death in part through what’s called cellular immunity. Immune cells – B and T cells – retain a memory of the vaccine and can start to attack the virus or make new antibodies that do so after 3 to 7 days. 

A booster might temporarily increase antibodies, but most of the protection conferred by those wanes within about four months, according to data from the North Carolina Department of Public Health. 

OUR IMMUNE SYSTEMS INSIST ON FIGHTING ORIGINAL VARIANT

Barouch thinks a better booster is possible. In a study published last week in Nature, he and colleagues showed that in monkeys, an inhaled vaccine had strong protection against infection, a nasal vaccine intermediate protection, and an injection very little or no protection. 

The invention of a vaccine that would directly protect the respiratory tract is “not far-fetched”, he says. There’s already an inhaled vaccine made by CanSino Bio on the market in China.

There’s another problem facing COVID-19 booster campaigns: The fast evolution of the virus and the stubborn tendency of our immune systems to insist on fighting the original variant, since that’s what we were first vaccinated against. 

This stubborn tendency is called imprinting, and may explain why so many fully vaccinated, multiple-boosted people have been infected by Omicron not just once but sometimes two or three times. It also explains data showing that the bivalent booster offered in 2022, with components of the initial strain and Omicron, didn’t produce any more Omicron-neutralising antibodies than the original booster. 

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BETTER BOOSTER VACCINES ARE POSSIBLE

The 2023 boosters don’t have the original strain – they are monovalent and aimed at the Omicron sub-variant XBB.1.5, which was dominant earlier in the year. Many scientists say this is a big improvement.

A study published last month in Nature showed that repeat exposures to Omicron through infection or Omicron-only booster shots can start to override the immune imprinting that has our immune systems stuck on the extinct original version of this virus.

Peking University researcher Yunlong (Richard) Cao, who headed the study, said exposure to Omicron generates what are called naive B cells, and over time these become tuned to fight Omicron. After two exposures, the body is better able to fight off future exposures to Omicron. 

As a caveat, he said, this study involved subjects in China who were very rarely exposed to the virus before Omicron, and who got a different kind of vaccine called an inactivated virus. Similar studies that followed people who got mRNA shots saw no overriding of the imprinting. 

Cao said the mRNA vaccines are more immunogenic than the ones used in China, which can make them more powerful but might render the imprinting effect stronger too. It might take people in the US and elsewhere more exposures to Omicron-only boosters or infections to retune their immune systems toward the new version of the virus – though the virus will continue to evolve as well.

The take-home message, he said, is that booster shots can have long-term impacts – and that we need to start thinking about how to battle this disease in the long term. We have multiple approved vaccines to explore and new ideas are coming from research labs all the time. We’re not ready to settle into a yearly boosting schedule with mRNA shots.

If people are sick and tired of anything, it’s getting COVID-19. If we had a new shot that kept us COVID-19-free for at least a year, more people would be willing to get it. 

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