evidence: Among the new mutations that BA.2.86 carries, 14 reside within an area of the spike protein called the receptor binding domain, which binds to the receptors on host cells. This suggests that BA.2.86 could have a greater capacity for infecting than its predecessor. In addition, the new sublineage, BA.2.86, is even more dissimilar when compared to the most recent sublineage, XBB.1.5, with 35 new mutations in the spike protein – including some unusual mutations – than to its precursor, BA.2. These alterations intrigue infectious disease specialists like me, and we are working to understand how they might affect this new variant’s behavior. [...] The emergence of BA.2.86 underscores the need for flexibility in current vaccine strategies to ensure continued effectiveness against these new variants. The newly FDA-approved fall 2023 COVID-19 booster shots are formulated to target XBB.1.5, which was dominant in early 2023 when public health officials made the reformulation decisions. The 2022 booster shot was designed to target both the original strain of SARS-CoV-2 as well as the BA.4 and BA.5 omicron lineages.