Future booster doses of COVID-19 are likely to require new formulations as new coronavirus variants are still emerging that raise concerns.

Having up-to-date information on COVID-19 vaccines means having three or four doses of the same dose at this time. The current boosters are the same formulations as the first permitted injections based on the original coronavirus strain, which appeared in late 2019. It still protects against serious COVID-19 disease, hospitalizations and deaths. But as immunity weakens over time and new, more contagious variants of SARS-CoV-2 emerge, the world needs a long-term strengthening strategy.

I am an immunologist who studies immunity to viruses. I was part of the teams that helped develop Moderna and Johnson & Johnson SARS-CoV-2 vaccines and monoclonal antibody therapies from Eli Lilly and AstraZeneca.

How many lines will eventually be filled in on your COVID-19 vaccination card?
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I am often asked how often or rarely I think people are likely to need a COVID-19 booster injection in the future. No one has a crystal ball to see which variant of SARS-CoV-2 comes next, or how good future variants will be in avoiding vaccine immunity. But the sight of other respiratory viral enemies that plague humanity for a while may suggest what the future might look like.

One example is the flu virus. It is endemic in humans, which means it has not disappeared and continues to cause recurring seasonal waves of infection in the population. Each year, officials try to predict the best formulations for flu shots to reduce the risk of serious illness.

As SARS-CoV-2 continues to evolve and is likely to become endemic, it is possible that people will need regular booster doses in the foreseeable future. I suspect that the researchers will eventually have to update the COVID-19 vaccine to adopt newer variants, as they do with the flu.

Influenza prediction based on careful monitoring

Influenza virus monitoring offers a potential model for monitoring SARS-CoV-2 over time. Influenza viruses have caused several pandemics, including the 1918 one, which killed an estimated 50 million people worldwide. There are seasonal outbreaks of influenza every year, and every year officials call on the public to be vaccinated against the flu.

Each year, health agencies, including the World Health Organization’s Global Influenza Surveillance System, make a qualified estimate based on the strains of influenza circulating in the Southern Hemisphere as to which of them are most likely to circulate in the forthcoming flu season in the Northern Hemisphere. Then begins large-scale production of vaccines based on selected influenza strains.

In some flu periods, the vaccine does not prove to be a great match for the virus strains that eventually circulate the most. In those years, the shot is not so good at preventing serious diseases. Although this prediction process is far from perfect, the field of influenza vaccines has benefited from strong viral surveillance systems and coordinated international efforts by public health agencies to prepare.

Although the details of influenza and SARS-CoV-2 viruses differ, I think that the COVID-19 area should consider adopting similar surveillance systems in the long term. Keeping track of the circulating strains will help researchers update the SARS-CoV-2 vaccine to match current coronavirus variants.

How SARS-CoV-2 has evolved so far

SARS-CoV-2 faces evolutionary difficulties as it reproduces and spreads from person to person. The virus needs to maintain its ability to enter human cells through its spike protein, while constantly changing the ways that it allows it to avoid immunity to the vaccine. Vaccines are designed to make your body recognize a particular top protein, so the more it changes, the higher the chance that the vaccine will be ineffective against the new variant.

Despite these challenges, SARS-CoV-2 and its variants have successfully evolved to be more transmissible and better avoid human immune responses. During the COVID-19 pandemic, a new dreaded variant of SARS-CoV-2 emerged, dominating the transmission in a series of waves every four to seven months. The D614G variant appeared almost like a watch in the spring of 2020 and surpassed the original SARS-CoV-2 outbreak. At the end of 2020 and the beginning of 2021, the alpha variant appeared and dominated the transmission. In mid-2021, the delta variant overtook the alpha and then dominated the transmission until it was pushed out by the omicron variant at the end of 2021.

There is no reason to think that this trend will not continue. In the coming months, the world may see a dominant descendant of various omicron subvariants. And it is certainly possible that a new variant will emerge from the non-dominant SARS-CoV-2 group, which is the way omicron itself came into being.

Current revaccinations are simply additional doses of vaccines based on an outbreak of the long-extinct SARS-CoV-2 virus. The coronavirus variants have changed a lot from the original virus, which does not bode well for the continued effectiveness of the vaccine. The idea of ​​annual custom injections – such as the flu vaccine – sounds tempting. The problem is that scientists have not yet been able to predict with certainty what the next variant of SARS-CoV-2 will be.

people walk near the tent marked
Regular booster doses may be in place for the foreseeable future.
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Planning for the future

Yes, the dominant SARS-CoV-2 variants in the coming fall and winter seasons may look different from the omicron subvariants currently in circulation. But an updated booster that more closely resembles today’s Omicron subvariants, along with the immunity that people already have from the first vaccines, is likely to offer better protection in the future. This may require less frequent strengthening – at least as long as the omicron sublines continue to dominate.

The Food and Drug Administration is due to meet in the coming weeks to decide what autumn boosters should be in time for manufacturers to produce injections. Vaccine manufacturers such as Moderna are currently testing their revaccination candidates in humans and evaluating the immune response against emerging variants. The test results are likely to determine what will be used in anticipation of the fall or winter waves.

Another option is to change the booster vaccine strategy to include universal coronavirus vaccine approaches, which already look promising in animal studies. Researchers are working on what is called a universal vaccine that would be effective against multiple strains. Some focus on chimeric spikes that bind parts of the spikes of different coronaviruses together in a single vaccine to enhance protective immunity. Others are experimenting with nanoparticulate vaccines, which allow the immune system to focus on the most vulnerable areas within the coronavirus peak.

These strategies have been shown to avert difficult-to-stop variants of SARS-CoV-2 in laboratory experiments. It also works in animals against the original SARS virus that caused the outbreak in the early 21st century, as well as against zoonotic coronaviruses from bats that could jump on humans and cause future SARS-CoV-3 outbreaks.

Science has provided several safe and effective vaccines that reduce the risk of serious COVID-19 disease. Reforming revaccination strategies, whether toward universal vaccines or upgraded revaccinations, can help lead us out of the COVID-19 pandemic.

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