Limited durability of protection conferred by XBB.1.5 vaccines against omicron-associated severe outcomes among community-dwelling adults, Ontario, Canada.

We estimated XBB.1.5 vaccine effectiveness (VE) against hospitalization/death among adults aged ≥50 years in Ontario, Canada, from September 2023 to June 2024. Compared with non-XBB.1.5 vaccinees, the initial protection at 0-3 months was 64 % (95 %CI, 57 %-69 %) during XBB-sublineage predominance. It was reduced to 57 % (95 %CI, 48 %-64 %) when JN/KP-sublineages became predominant, and quickly declined. No significant protection was observed >6 months post-vaccination. The VE estimates were lower when the last vaccine dose in the reference group was given more recently than 12 months, or was the omicron-containing bivalent vaccine. Short durability of protection poses unique challenges for COVID-19 vaccination.