The UK-based COV-Boost trial has found that fourth doses of messenger RNA (mRNA) vaccines give people even higher levels of protective antibodies against SARS-CoV-2 than they gained from their third dose (Lancet Infect. Dis. 2022, DOI: 10.1016/S1473-3099(22)00271-7). The trial research team, led by Saul Faust of the University of Southampton, measured antibody levels and immune cell activation in 133 participants after they received either a full dose of BioNTech and Pfizer’s Comirnaty vaccine or a half dose of Moderna’s Spikevax as a fourth vaccination. The trial participants had all received a Comirnaty booster at least 7 months before. The researchers recorded any side effects participants experienced after the new booster and measured antibody and T-cell levels at the time of the shot and 14 days later. Participants had even more antibodies targeting the spike protein than they had after the third dose—meaning that fourth doses don’t just top up immunity but increase it. The boosting benefit was less pronounced for those in the study who had retained high antibody levels from their third dose. According to the COV-Boost team, this finding hints that there may be a ceiling to vaccine-acquired immunity with current vaccines. More studies will be needed to determine that. More importantly, Faust said at a press conference, fourth doses “produce a substantial boost to both the antibody and cellular immunity.” The COV-Boost study will monitor the trial cohort to see how the immunity changes over time.