COVID super-immunity: One of the pandemic’s great puzzles

Initial studies of people with hybrid immunity found that their serum — the antibody-containing portion of blood — was far better able to neutralize immune-evading strains, such as the Beta variant identified in South Africa, and other coronaviruses, compared with ‘naive’ vaccinated individuals who had never encountered SARS-CoV-22. It wasn’t clear whether this was just due to the high levels of neutralizing antibodies, or to other properties.

The most recent studies suggest that hybrid immunity is, at least partly, due to immune players called memory B cells. The bulk of antibodies made after infection or vaccination come from short-lived cells called plasmablasts, and antibody levels fall when these cells inevitably die off. Once plasmablasts are gone, the main source of antibodies becomes much rarer memory B cells that are triggered by either infection or vaccination.

Some of these long-lived cells make higher-quality antibodies than plasmablasts, says Michel Nussenzweig, an immunologist at the Rockefeller. That’s because they evolve in organs called lymph nodes, gaining mutations that help them to bind more tightly to the spike protein over time. When people who recovered from COVID-19 are re-exposed to SARS-CoV-2’s spike, these cells multiply and churn out more of these highly potent antibodies.