Pre-Existing Immune Cell Memory That Recognizes Common Cold Coronaviruses Could Also Recognize and Fight off SARS-CoV-2

This immune cell memory gives the cells a head start in recognizing and fighting off repeat invaders. The research by LJI scientists that could explain why some people have milder COVID-19 cases than others builds on a recent study which showed that 40 to 60% of people never exposed to SARS-CoV-2 had T cells that reacted to the virus. Their immune systems recognized fragments of the virus it had never seen before. This finding turned out to be a global phenomenon and was reported in people from the Netherlands, Germany, the UK and Singapore. Scientists have wondered if these T cells came from people who had previously been exposed to common cold coronaviruses, also termed as SARS-CoV-2’s “less dangerous cousins.” If so, was exposure to these cold viruses leading to immune memory against SARS-CoV-2?

For the new study, the LJI scientists relied on a set of samples collected from study participants who had never been exposed to SARS-CoV-2. They defined the exact sites of the virus that are responsible for the cross-reactive T cell response. Their analysis showed that unexposed individuals can produce a range of memory T cells that are equally reactive against SARS-CoV-2 and four types of common cold coronaviruses. This discovery suggests that fighting off a common cold coronavirus can indeed teach the T cell compartment to recognize some parts of SARS-CoV-2 and provides evidence for the hypothesis that common cold viruses can, in fact, induce cross-reactive T cell memory against SARS-CoV-2. Looking closer, the researchers found that while some cross-reactive T cells targeted the SARS-CoV-2’s spike protein, the region of the virus that recognizes and binds to human cells, pre-existing immune memory was also directed to other SARS-CoV-2 proteins. This finding is relevant, as most vaccine candidates target mostly the spike protein. These findings suggest the hypothesis that inclusion of additional SARS-CoV-2 targets might enhance the potential to take advantage of this cross reactivity and could further enhance vaccine potency.

“We knew there was pre-existing reactivity, and this study provides very strong direct molecular evidence that memory T cells can ‘see’ sequences that are very similar between common cold coronaviruses and SARS-CoV-2,” said LJI Professor Alessandro Sette, Dr. Biol. Sci. who co-led the new study.

“We have now proven that, in some people, pre-existing T cell memory against common cold coronaviruses can cross-recognize SARS-CoV-2, down to exact molecular structures,” said LJI Research Assistant Professor Daniela Weiskopf, Ph.D.. “This could help explain why some people show milder symptoms of disease while others get severely sick.”.

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La Jolla Institute for Immunology