Since late 2022, the share of infections caused by the SARS-CoV-2 lineage XBB. 1.5 has gradually increased in the United States, resulting in XBB. 1.5 becoming the dominating SARS-CoV-2 lineage in the United States and a similar trend is likely to soon take place also in European countries. However, information on the virological properties of XBB. 1.5 is scarce. Here, we conducted an initial virological assessment of the SARS-CoV-2 XBB. 1.5 lineage.

The SARS-CoV-2 XBB lineage possesses an extraordinarily high capacity for antibody evasion due to its unique set of S protein mutations [1–4]. However, this trait may have come at the cost of a moderately reduced host cell entry efficiency as suggested by recent in vitro data [1, 5], which may explain why infections caused by XBB sublineages only accounted for a small proportion of total SARS-CoV-2 infections in several countries (except India) so far (Fig. 1 a). Recently, this trend has changed for the United States, where the share of infections caused by SARS-CoV-2 sublineage XBB. 1.5 has gradually increased since late 2022, and XBB. 1.5 now represents the dominating SARS-CoV-2 lineage (Fig. 1 a). Moreover, although being presently detected at low frequencies only, a similar increase in the share of XBB. 1.5-related infections is also observed for European countries (Fig. 1 a). The XBB. 1.5 S protein differs by only one mutation (S486P) from the S protein of the parental XBB. 1 lineage, and this mutation is located in the receptor-binding domain (RBD)(Fig. 1 b). Thus, it may affect transmissibility by modulating cell entry efficiency, and may alter sensitivity to antibody-mediated neutralization. Here, we performed an assessment on the host cell entry efficiency of the SARS-CoV-2 XBB. 1.5 lineage and its sensitivity to antibody-mediated neutralization, using S protein-bearing pseudovirus particles (pp), which are a suitable model system for the analysis of SARS-CoV-2 host cell entry and its neutralization [6]. Particles pseudotyped with the S protein of the ancestral B. 1 lineage (B. 1pp) or Omicron sublineages BA. 4/BA. 5 (identical on amino acid level, BA. 4-5pp), BQ. 1.1 (BQ. 1.1pp), or XBB. 1 (XBB. 1pp) were used for comparison. First, we compared cell line tropism and host cell entry efficiency of the different pseudoviruses. As expected, BA. 4-5pp displayed augmented cell entry efficiency compared to B. 1pp for most cell lines tested with the exception