COVID-19 vaccines don’t pack their usual punch in people who get boosted shortly after an infection1.

People who catch SARS-CoV-2 before vaccination develop especially strong immune defences against the virus. To learn whether this ‘hybrid immunity’ depends on the timing between infection and boosting, Clarisa Buckner at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and her colleagues tracked 66 people, who had a variety of histories of vaccination and infection, after they received a third dose of an mRNA vaccine based on the virus’s spike protein.

In the 60 days after boosting, most participants’ antibody responses against variants old and new grew stronger. But participants who had been infected less than 180 days before their boost had a weaker antibody response to the third dose than did those with infections more than 180 days in the past. The latter had responses as good as those of people who hadn’t been infected before the boost.

Analysis of participants’ antibody-making B cells suggested that a short window between infection and boosting did not allow enough time for some of these cells to return to an ideal state for another tussle with the spike protein.