SummaryBackgroundLike its predecessors in the XBB family, XBB.1.5 is highly immune evasive from therapeutic monoclonal antibodies and neutralizing antibodies generated by vaccination and/or infection. However, there is a lack ofin vivodata on XBB.1.5 in animal models such as Syrian hamsters.MethodsSyrian hamsters (females) were used to examine airborne transmission along with virus replication of XBB.1.5 in naïve animals and human ACE2 hamsters with pre-existing immunity from a previous infection with Omicron BA.1. Assays were performed to determine neutralizing antibody responses, and virus titers were determined by standard plaque assays.FindingsUnlike earlier Omicron subvariants, such as BA.1 and BA.2, XBB.1.5 transmitted more efficiently in the hamster model. In addition, XBB.1.5 partially escaped BA.1-immunity from a previous infection with XBB.1.5 replicating in the nasal turbinate tissues and to a lesser extend in the lung tissues of previously infected hamsters.InterpretationOurin vivodata showing better airborne transmissibility of the Omicron subvariant XBB.1.5 than its predecessor, BA.2, in Syrian hamsters will allow researchers to further investigate amino acid substitutions that give XBB.1.5 a fitness advantage over BA.2 in transmission, data that may be important in studies of SARS-CoV-2 transmission in humans.FundingThis research is supported by grants from theCenter for Research on Influenza Pathogenesis and Transmission(CRIPT; 75N93021C00014), funded by the10.13039/100000060National Institute of Allergy and Infectious Diseasesand by aResearch Program on Emerging and Reemerging Infectious Diseases(JP21fk0108552 and JP21fk0108615), aProject Promoting Support for Drug Discovery(JP21nf0101632), theJapan Program for Infectious Diseases Research and Infrastructure(JP22wm0125002), and The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) grant (JP223fa627001) from the10.13039/100009619Japan Agency for Medical Research and Development.