Must COVID-19 vaccines need to be regularly readjusted in the future?

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Pedigrees of coronavirus 229E and influenza virus H3H2

Flu vaccines need to be updated every year to protect against new influenza viruses. Will this also be necessary for COVID-19 vaccines? To estimate this, a research team from Charité – Universitätsmedizin Berlin compared the evolution of common cold coronaviruses with that of flu viruses. The researchers‘ prognosis: Regular vaccine updates will be necessary during the pandemic, but after a few years a longer shelf life of the vaccines can be expected. The study was published in the journal Virus Evolution*.

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Influenza viruses are masters at evading the human immune response: They change so quickly that the antibodies the immune system has produced after a previous infection or vaccination can no longer recognise them well. This makes it necessary to make elaborate adjustments to the vaccine in practically every flu season. SARS-CoV-2 has also already produced various mutants, some of which, like the so-called South African variant, partially subvert the immune response. The first vaccine manufacturers are therefore already developing new versions of their vaccine. What does this mean for the future? Will COVID-19 vaccines, like flu vaccines, need to be updated regularly?

In order to be able to assess whether SARS-CoV-2 will show as strong a „flight“ from the immune system in the long term as influenza viruses, virologists at the Charité have studied the genetic development of cold coronaviruses. Four such comparatively harmless coronaviruses are known, which cause around 10 per cent of colds worldwide and have been circulating in humans for much longer than SARS-CoV-2. They also hijack human cells via the so-called spike protein, which forms the eponymous „crown“ on the surface of the virus and against which all COVID-19 vaccines to date have been directed.

For the study, the research team traced how the spike gene of the two longest-known coronaviruses 229E and OC43 has changed over the past 40 years. To do this, the scientists compared the sequences from samples of different ages that had been deposited in a gene database and developed a family tree for both coronaviruses based on the mutations that had arisen over time. For comparison, the researchers looked at the influenza strain H3N2, which is particularly efficient at evading the human immune response.

The calculated phylogenetic trees of both the coronaviruses and the influenza virus had one thing in common: they showed a pronounced staircase shape. „Such an asymmetric phylogenetic tree means that one circulating viral lineage is regularly replaced by another because it has a survival advantage,“ explains Dr Wendy K. Jó, first author of the study from the Institute of Virology at Charité. „This is an indication of so-called antigenic drift, i.e. a continuous change in surface structures by which viruses evade the human immune response. The indigenous coronaviruses therefore escape the immune system just like the flu virus. However, one must additionally look at the speed at which this evolution occurs.“

To do this, the research team determined the evolution rates of the three viruses. While the influenza sequence accumulated 25 mutations per 10,000 genetic building blocks per year, the coronaviruses only had about six mutations. This means that the common coronaviruses changed four times slower than the influenza virus. „With regard to SARS-CoV-2, this is good news,“ sums up Prof. Dr Christian Drosten, Director of the Institute of Virology and scientist at the German Centre for Infection Research (DZIF).

The evolutionary speed of SARS-CoV-2 is currently estimated at around ten mutations per 10,000 genetic building blocks per year, which is significantly higher than that of common coronaviruses. „This rapid genetic change of SARS-CoV-2 is reflected in the emergence of many different virus variants worldwide,“ explains Prof. Dr Jan Felix Drexler, head of the study from the Institute of Virology and DZIF researcher. „However, the reason for this lies mainly in the high incidence of infections during the pandemic: where there are many infections, a virus can also evolve more quickly. Based on the evolution rates of the indigenous cold coronaviruses, we assume that SARS-CoV-2 will also change more slowly as soon as the infection event subsides – i.e. after a large part of the global population has built up immune protection either through the disease itself or through vaccination. Therefore, we assume that COVID-19 vaccination will need to be reviewed regularly during the pandemic and adjusted if necessary. However, once the situation has stabilised, the vaccines are expected to be usable for longer.“

*Jo WK et al. The evolutionary dynamics of endemic human coronaviruses. Vir Evol 2021. doi: 10.1093/ve/veab020

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Institut für Virologie

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