Covid-19 vaccines should target only omicron for best immune response


The omicron variant is dominant worldwide, prompting many countries to adapt their vaccine response

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“Bivalent” covid-19 vaccines based on proteins from the initial SARS-CoV-2 coronavirus as well as the more recent omicron variant may be less effective than those that just target omicron, a study suggests.

The findings come not from a randomised trial, the best kind of medical evidence, but from studying people’s responses to natural infections.

Bivalent vaccines are being offered in several countries, including the UK, Australia, New Zealand and Canada. In the US, however, the vaccines on offer are based just on the omicron variant.

The first vaccines used during the covid-19 pandemic were based on the “spike” protein of the original coronavirus strain that started spreading worldwide in early 2020.

By the end of 2021, however, the first omicron variants arrived, quickly displacing the previous ones. Omicron was so different that a lot of people started getting infected by it despite being vaccinated against the original virus, although the vaccines still worked well at reducing deaths and hospitalisations.

Around the world, many people’s SARS-CoV-2 antibodies are subtly different because they are fine-tuned to the virus spike proteins they have encountered so far, whether in the form of infections or vaccines.

There have been fears that people’s antibodies would be so optimised to the original version of the virus that it would limit their immune response to omicron and future variants. It isn’t clear why this phenomenon – known as immune imprinting – happens, but it has been observed with other viruses, such as flu.

Now, Yunlong Cao at Peking University in Beijing and his colleagues have shown that among people in China, two natural exposures to omicron after a dose of an ancestral vaccine redirected their immune cells to make more omicron-specific antibodies. This suggests we could mimic these natural exposures via omicron-only vaccines.

“This paper says very clearly there’s no need to keep the original [protein] in the vaccine – it doesn’t harm, but it doesn’t drive the immune response towards omicron,” says Georg Behrens at Hanover Medical School in Germany. “If we want to go further towards omicron, you need an omicron-only vaccine.”


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