Giuseppe Michieli
BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies
Author summary SARS-CoV-2 variants are under selection pressure to evolve in the presence of humoral and T-cell immunity from vaccination and or natural infections. Newer variants of the SARS-CoV-2 Omicron and its sub-lineages have emerged in the current year with each of the variants harboring additional mutations primarily in the spike region to enhance infectivity and transmission and also to escape neutralization from pre-existing antibodies. We show here that the BA.1, BA.2 and BA.2.75 sub-lineages of the Omicron variant have comparable or relatively better capacity for viral entry. However, despite comparable kinetics of replication, the omicron sub-lineages have compromised ability to disrupt the epithelial barrier in lung epithelial cell lines. These newer variants have accumulated several unique mutations in the spike region to escape from humoral immunity and our data suggests that BA.2.75 is the most antibody evasive variant. Both the Delta and the Omicron variants were inhibited by copper and iron salts thus providing an option for supplementation trials in SARS-CoV-2 patients. Overall, the evolution of SARS-CoV-2 is geared towards optimizing viral entry, replication and immune evasion which may favor attaining endemic status due to reduced pathogenicity.
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