LAUSR

Waning antibodies and rapidly emerging variants are challenges for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine development. Adjusting existing immunization schedules and further boosting strategies are under consideration. Here, the immune responses induced by an alum‐adjuvanted inactivated SARS‐CoV‐2 vaccine in mice were compared among immunization schedules with two or three doses. For the two‐dose schedule, a 0–28‐day schedule induced 5‐fold stronger spike‐specific IgG responses than a 0–14‐day schedule, with only a slight elevation of spike‐specific cellular immunity 14 days after the last immunization. A third homologous boost 2 or 5 months after the second dose for the 0–28‐day schedule slightly strengthened humoral responses (1.3‐fold for the 0–1–3‐month schedule, and 1.8‐fold for the 0–1–6‐month schedule) 14 days after the last immunization. Additionally, a third homologous boost (especially with the 0–1–3‐month schedule) induced significantly stronger cell‐mediated immunity than both two‐dose immunization schedules for all indexes tested, with a response similar to that induced by a one‐dose heterologous boost with BNT162b2 in clinical trials, according to cellular immunity analysis (1.5‐fold). These T cell responses were Th2 oriented, with good CD4+ and CD8+ memory. These results may offer clues for applying a homologous boosting strategy for alum‐adjuvanted inactivated SARS‐CoV‐2 vaccines.