T cell targeting SARS-CoV-2 viruses. Credit: selvanegra/ iStock / Getty Images Plus.
A group of immune white blood cells called T-cells, produced in the body after being infected with a SARS-CoV-2 variant, play a key role in preventing re-infection from a different variant, according to a study led by Matteo Iannacone from the San Raffaele scientific Institute in Milan1. This goes against the prevailing view according to which it is mostly neutralizing antibodies that prevent infection, while T-cells are mostly involved in protecting the body from the severe forms of the disease2.
“We are fans of antibodies, and we believe that vaccines against COVID-19 are the most effective tools to contrast the pandemic,” Iannacone says, “but they wane quite rapidly, and they lose efficacy when the virus mutates significantly.”On the other hand, T-cells are known to persist in the blood for as long as one year after infection or vaccination, and to be more robust with respect to virus evolution. While antibodies prevent the virus from entering the host’s cells, T cells activate once it has entered the cells and eliminate them. If this happens fast enough the virus remains undetectable, and the infection is tamed.
The authors compared two groups of transgenic mice, both engineered to modify their ACE2 receptor. “The murine ACE2 receptor does not bind as efficiently to SARS-CoV-2 as the human one,” explains Valeria Fumagalli, researchers at San Raffaele scientific Institute and first author of the study. “We used CRISPR-Cas9 to introduce minimal changes to the ACE2 murine receptor and improve its affinity with SARS-CoV-2”.The two groups differed in their capacity to produce antibodies. One group had a complete and functioning immune system, the other one could not produce antibodies, while retaining normal B and T cells. “Preserving the physiological structure of lymphoid organs, and functioning B cells is essential to have a non-defective response of T cells,” Iannacone explains.
The mice were initially exposed to the Delta variant, the one that emerged in the summer of 2021. One month after, they were exposed to the Omicron variant, which emerged in late 2021. Surprisingly, not only the mice that produced antibodies against Delta resisted the infection, but so did the ones with no antibodies: the authors were unable to detect any viral RNA in their nose and lungs.
“Our results, together with those obtained in primates and real-world epidemiological data, suggests that T-cells produced after previous infections or vaccinations protect from getting infected again,” Iannacone comments. He adds that this could mean that three vaccine doses could be enough for young and healthy people, and hopes that the study also encourages the development of assays which allow to monitor T cells response in large populations.
