We can’t keep using the same formula in COVID-19 shots

(ORDO NEWS) — A current COVID-19 vaccine means that you have received three or four doses of the same vaccine so far. The current boosters are the same formulations as the first legal shots, based on the original coronavirus strain that emerged in late 2019. They still protect against severe COVID-19, 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 strategy to boost immunity.

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

I am often asked how often or how infrequently I think people will need COVID-19 boosters in the future. No one has a crystal ball to see which SARS-CoV-2 variant will emerge next or how well future variants will evade vaccine immunity.

But if we turn to other respiratory viruses that have plagued humanity for some time, we can imagine what the future might be like.

An example is the influenza virus. It is endemic to humans, meaning it has not disappeared and continues to cause recurring seasonal waves of infection in the population. Every year, officials try to predict the optimal formulation of a flu shot to reduce the risk of severe illness.

As SARS-CoV-2 continues to evolve and is likely to become endemic, people may need periodic booster shots for the foreseeable future. I suspect scientists will eventually have to update the COVID-19 vaccine to deal with new variants, as they do with the flu.

Predicting influenza based on careful observation

Influenza surveillance provides a potential model for how SARS-CoV-2 can be tracked over time. Influenza viruses have caused several pandemics, including one in 1918 that killed an estimated 50 million people worldwide. There are seasonal flu outbreaks every year, and every year officials encourage the public to get flu shots.

Each year, health authorities, including the World Health Organization’s Global Influenza Surveillance and Response System, make an informed guess based on the strains of influenza circulating in the Southern Hemisphere which are most likely to circulate in the coming Northern Hemisphere influenza season. Then large-scale production of vaccines based on selected influenza strains begins.

In some flu seasons, the vaccine is not well suited to the strains of the virus that end up circulating most widely. In such years, vaccination is not so good at preventing serious diseases.

While this forecasting process is far from perfect, influenza vaccination has benefited from strong viral surveillance systems and concerted international health efforts to prepare.

Although the characteristics of influenza viruses and SARS-CoV-2 are different, I think that in the field of COVID-19, consideration should be given to implementing similar surveillance systems in the long term. Keeping an eye on which strains are circulating will help researchers update the SARS-CoV-2 vaccine to match current coronavirus variants.

How SARS-CoV-2 has evolved so far

In the process of reproducing and spreading from person to person, SARS-CoV-2 faces an evolutionary challenge. The virus needs to retain the ability to enter human cells with its spike protein and at the same time change in such a way as to bypass vaccine immunity.

Vaccines are designed to make the body recognize a particular protein, so the more it changes, the more likely it is that the vaccine will be ineffective against the new variant.

Despite these challenges, SARS-CoV-2 and its variants have successfully evolved to become more transmissible and better evade the immune response of humans.

During the COVID-19 pandemic, a dangerous new variant of SARS-CoV-2 has emerged and has come to dominate transmission in a series of waves of infection every four to seven months.

Almost like clockwork, the D614G variant emerged in the spring of 2020 and overtook the original strain of the SARS-CoV-2 outbreak. In late 2020 and early 2021, an alpha variant emerged that dominated transmission of the virus.

In mid-2021, the delta variant overtook the alpha variant and then dominated transmission of the virus until it was superseded 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 offspring of various omicron sub-variants. And it’s certainly possible that a new variant will emerge from the non-dominant pool of SARS-CoV-2 – which is how the omicron itself came to be.

The current booster shots are simply additional doses of vaccines based on an outbreak of a strain of the SARS-CoV-2 virus that has long since died out. Variants of the coronavirus have changed a lot from the original virus, which does not bode well for the continued effectiveness of the vaccine.

The idea of ​​making individual annual shots – like the flu vaccine – sounds appealing. The problem is that scientists cannot yet predict with certainty what the next variant of SARS-CoV-2 will be.

Planning for the future

Yes, the dominant SARS-CoV-2 variants in the upcoming fall and winter seasons may differ from the omicron subvariants currently circulating.

But an updated booster more similar to today’s Omicron sub-variants, combined with the immunity people already have from the first vaccines, will likely provide better protection in the future. This may require less frequent revaccination – at least as long as omicron subvariations continue to dominate.

In the coming weeks, the Food and Drug Administration will hold a meeting to decide what the fall boosters should be like so manufacturers can get those shots out. Vaccine manufacturers such as Moderna are currently testing their booster candidates in humans and evaluating the immune response against new variants. The results of the trials will likely decide what will be used ahead of the fall or winter spike in cases.

Another possibility is to change the vaccination strategy to include universal coronavirus vaccines, which already look promising in animal studies. Researchers are working on a so-called universal vaccine that would be effective against multiple strains.

Some are focusing on chimeric spikes, which combine parts of spikes from different coronaviruses in one vaccine to expand protective immunity. Others are experimenting with nanoparticle vaccines that force the immune system to focus on the most vulnerable areas of the coronavirus spike.

In laboratory experiments, these strategies have been shown to prevent hard-to-stop variants of SARS-CoV-2. They also work in animals against the original SARS virus that caused the outbreak in the early 2000s, as well as against zoonotic bat coronaviruses that could pass to humans, causing a future outbreak of SARS-CoV-3.

Science has developed many safe and effective vaccines that reduce the risk of severe COVID-19. Revisiting booster strategies – either towards universal vaccines or updated boosters – could help us avoid the COVID-19 pandemic.


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