Two studies suggest that ‘breakthrough’ SARS-CoV-2 infections result in improved immune protection against multiple variants of the virus, and data from one of the studies indicates that such infections also protect against Omicron1,2.
Researchers have previously shown that people who have caught SARS-CoV-2 and are later vaccinated tend to make high levels of antibodies against the SARS-CoV-2 spike protein, one of the immune system’s main targets when it is fending off the virus. These individuals’ blood serum — which contains antibodies — blocks a diverse array of SARS-CoV-2 variants, and does so more effectively than serum from vaccinated people who were never infected and serum from people whose immunity comes from infection only.
But it has been unclear whether this powerful ‘hybrid immunity’ is also generated in people who were vaccinated before being infected.
Microbiologist Fikadu Tafesse at Oregon Health & Science University in Portland and his colleagues analysed serum from three groups of health-care workers: some who’d had breakthrough infections, others who’d been infected before they were vaccinated, and vaccinated people with no history of infection. In laboratory assays, the sera from both groups with previous infections had higher levels of antibodies against the spike protein than did serum from people protected only by vaccines. The sera from infected people were also highly effective at protecting cells from infection by variants including Alpha, Beta and Delta, although the team has not yet looked at activity against Omicron. The researchers report their work in a 25 January study in Science Immunology1.
Those results chime with a 19 January Cell study2 led by structural biologists Alexandra Walls and David Veesler, both at the University of Washington in Seattle. This team looked at people who’d been infected and then received two doses of vaccine; people who had two doses of vaccine and then experienced breakthrough infections; and people who’d had a third, booster vaccine dose but no infection. Serum levels of antibodies that blocked variants including Omicron were higher, and persisted for longer, in all three groups than in people who’d had two doses of vaccine and hadn’t been infected.
The maths of COVID-19 protection
The researchers suggest that the number of times people are exposed to SARS-CoV-2, whether through vaccination, infection or both, is a key factor in the quality of their antibody response. Confirming that idea, the group found that eight individuals whose immune systems had ‘seen’ the SARS-CoV-2 spike protein four times — once during a 2020 infection and again during three separate vaccinations — had especially strong antibody responses against several variants, and even against the virus behind the 2002–04 epidemic of severe acute respiratory syndrome. “Those individuals are clearly doing the best,” says Veesler.
Danny Altmann, an immunologist at Imperial College London, says it will be important to compare breakthrough infections caused by different variants. Current vaccines are based on the spike protein from the version of the virus first identified in Wuhan, China, in 2020, and vaccine-induced immune responses after a breakthrough infection will probably differ from variant to variant. Most of the breakthrough infections studied by Walls and Veesler’s team were caused by Delta, but they also plan to analyse samples from people who have experienced a breakthrough infection caused by Omicron.
With Omicron driving a global surge in cases, understanding the immunity that follows breakthrough infections is important, because it will affect many people, says Tafesse. “There is so much virus in circulation in the community. There is a high chance we’ll all get a breakthrough infection.”
doi: https://doi.org/10.1038/d41586-022-00328-8
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