Decisive conditions for strategic vaccination against SARS-CoV-2.

While vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV-2) are being administered, in many countries it may still take months until their supply can meet demand. The majority of available vaccines elicit strong immune responses when administered as prime-boost regimens. Since the immunological response to the first ("prime") dose may provide already a substantial reduction in infectiousness and protection against severe disease, it may be more effective-under certain immunological and epidemiological conditions-to vaccinate as many people as possible with only one dose instead of administering a person a second ("booster") dose. Such a vaccination campaign may help to more effectively slow down the spread of SARS-CoV-2 and reduce hospitalizations and fatalities. The conditions that make prime-first vaccination favorable over prime-boost campaigns, however, are not well understood. By combining epidemiological modeling, random-sampling techniques, and decision tree learning, we find that prime-first vaccination is robustly favored over prime-boost vaccination campaigns even for low single-dose efficacies. For epidemiological parameters that describe the spread of coronavirus disease 2019 (COVID-19), recent data on new variants included, we show that the difference between prime-boost and single-shot waning rates is the only discriminative threshold, falling in the narrow range of 0.01-0.02  day-1 below which prime-first vaccination should be considered.