Will COVID-19 vaccines need to be adapted regularly?

Influenza vaccines should be evaluated annually to ensure that they remain effective against new influenza viruses. Will the same be true for COVID-19 vaccines? In order to assess whether and to what extent this may be necessary, a team of researchers from Charité – Universitätsmedizin Berlin compared the evolution of endemic coronaviruses of the “ common cold ” to that of influenza viruses. Researchers predict that while the pandemic is ongoing, vaccines will need to be regularly updated. A few years after the onset of the post-pandemic period, however, the vaccines are likely to remain effective for longer. This study was published in Evolution of the virus*.

Influenza viruses are masters of evading the human immune system. They undergo changes so rapidly that the antibodies produced by the immune system in response to an infection or a previous vaccination become unable to neutralize them. Therefore, the complex task of evaluating and updating the seasonal influenza vaccine must be repeated every year. Mutations within SARS-CoV-2 have already produced a number of variants, some of which (like the South African variant) partially elude the body’s immune response. As a result, some vaccine manufacturers have already started to develop new versions of their vaccines. What does this mean for the future? Will COVID-19 vaccines mirror influenza vaccines by requiring regular updates?

In order to assess whether, in the long term, SARS-CoV-2 is likely to demonstrate an immune evasion capacity comparable to that of influenza viruses, the Charité virologists studied the genetic evolution of the four coronaviruses of the “ common cold ” currently known. These relatively harmless coronaviruses are known to be responsible for around 10% of common colds worldwide and are circulating in humans much longer than SARS-CoV-2. Much like SARS-CoV-2, they enter human cells with the help of “spike protein,” a surface protein that gives the virus its signature, crown-shaped appearance (and name). The spike protein is also the target of all current COVID-19 vaccines.

For their study, the researchers focused on the two oldest coronaviruses (called 229E and OC43), tracing changes in the spike gene about 40 years in the past. The researchers began by comparing the sequences of a range of old samples that had been deposited in a DNA sequence database. Based on the mutations that appeared over time, they then produced phylogenetic trees for the two coronaviruses. The researchers compared their findings with the phylogenetic tree of H3N2, an influenza subtype particularly effective at evading the human immune response.

The researchers’ calculations revealed a feature common to the phylogenetic reconstructions of the coronaviruses and the influenza virus: all three had a pronounced ladder shape. “An asymmetric tree of this type is likely the result of the repeated replacement of one variant of the circulating virus with another that had a fitness advantage,” says the study’s first author, Dr. Wendy K. Jó of the Institute of Virology of Charité. “This is evidence of ‘antigenic drift,’ an ongoing process involving changes in surface structures that allow viruses to evade the human immune response. This means that these endemic coronaviruses also elude the immune system, while like the flu virus. has to look at the speed with which this evolutionary adaptation occurs. “

For this step, the researchers determined the rates of evolution of the three viruses. While the influenza virus accumulated 25 mutations per 10,000 nucleotides (genetic building blocks) per year, coronaviruses accumulated around 6 such mutations over the same period. The rate of change of endemic coronaviruses was therefore four times slower than that of the influenza virus. “Regarding SARS-CoV-2, this is good news,” summarizes Prof. Dr Christian Drosten, director of the Institute of Virology and researcher at the German Center for Research on Infections (DZIF).

SARS-CoV-2 is currently estimated to change at a rate of around 10 mutations per 10,000 nucleotides per year, which means that the rate at which it evolves is significantly higher than that of endemic coronaviruses. “This rapid genetic change in SARS-CoV-2 results in the emergence of many viral variants around the world”, explains Professor Jan Felix Drexler, director of the study, researcher at the Institute of Virology and DZIF . “This, however, is likely due to the high rates of infection seen during the pandemic. When the number of infections is so high, a virus is able to evolve more rapidly. Based on the rates of evolution observed in the endemic coronavirus of the common cold, we are hoping that SARS-CoV-2 will start to change more slowly once infections start to subside – that is, once a large portion of the world’s population has developed a disease. immunity either as a result of infection or by vaccination. We therefore expect that COVID-19 vaccines will need to be monitored regularly throughout the pandemic and updated as necessary. Once the situation stabilizes, vaccines are likely to stay effective longer. “

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

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