This makes it difficult to know whether vaccine developers are really on the right track. Their guess is mainly based on how the immune system reacts to other pathogens. However, some viruses evade typical patterns. They short the immune response. The most notorious example, according to Wherry, is HIV, which attacks the T cells that would coordinate the immune response to the virus. SARS-CoV-2 has already offered its own twists, as well as its propensity to trigger out of control immune responses. For Covid-19 there is “no prototypical immune response, especially in severe cases,” says Wherry.
Recently, however, systematic studies of T and B cell responses to SARS-CoV-2 have begun to elicit some patterns. Researchers at the La Jolla Institute of Immunology recently investigated T cell responses in “average”
Just having T cells – or even antibodies – that recognize the virus doesn’t mean you’re protected. There’s a lot more to learn about that. But the results looked like good news in the vaccine. “That confirms it [helper] T cells will be an important factor in generating a robust antibody response, ”says Permar. This is a relief for pharmaceutical companies trying to repeat this process with a vaccine.
But immunology is never easy, do you remember? The results of the La Jolla group were associated with wrinkles: in a control group of blood donors who had never been exposed to SARS-CoV-2, the researchers also found T cells that recognized the virus. They speculate that these T cells could be “cross-reactive” with other viruses. Suppose you had a lot of colds – especially colds caused by other corona viruses. Then your immune system may be ready to recognize this new virus based on its experience with other viral proteins, the researchers suggested.
It is still too early to determine whether these special T cells offer useful protection against SARS-CoV-2, the researchers warn. (Let’s just make the blanket restriction for now.) But cross-reactive cells could also affect vaccines, Permar says. These T cells could be a good thing if they give their carriers a head start in the production of antibodies after vaccination. Or they could backfire if a vaccine stimulates them to produce the wrong type of antibody, which leads to a more accurate response to SARS-CoV-2.
And what if these antibodies decrease in exposed people or if they don’t show up at all? To answer this question, Buggert’s team in Sweden took a slightly different approach. In addition to Covid-19 patients and two control groups – blood donors who gave samples before and after the pandemic started – they added members from the households of people with known cases. They argued that even if they had never shown or tested symptoms, they were more likely to be exposed to the virus than the general population.
Like other researchers, Buggert’s team saw cross-reactive T cells in unexposed people. However, they also looked for responses specific to this virus by identifying a unique set of viral proteins that recognized these T cells – a response that was not seen in pre-pandemic blood donors. “People who were really infected [with SARS-CoV-2] tend to react against several different regions of the virus, ”explains Buggert. “You have a broader answer.” In some blood donations during the pandemic and in household members of Covid-19 patients, they found this unique T cell response, but no antibodies.