Talk abstracts
Talk on Tuesday 04:45-05:00pm submitted by Julia Faraone
Neutralization and fusogenicity of SARS-CoV-2 Omicron XBB variant
Julia N Faraone (Center for Retroviruses and Department of Veterinary Biosciences, The Ohio State University), Panke Qu, John P Evans, Yi-Min Zheng, Claire Carlin, Mirela Anghelina (Center for Retroviruses and Department of Veterinary Biosciences, The Ohio State University), Patrick Stevens, Soledad Fernandez, Daniel Jones, Gerard Lozanski (Center for Retroviruses and Department of Veterinary Biosciences, The Ohio State University), Ashish Panchal, Linda J Saif, Eugene M Oltz, Richard J Gumina (Center for Retroviruses and Department of Veterinary Biosciences, The Ohio State University), Shan-Lu Liu (Center for Retroviruses and Department of Veterinary Biosciences, The Ohio State University)
Abstract:
The emergence of the Omicron variant of SARS-CoV-2 in 2021 caused widespread concern due to its large amount of spike mutations. These spike mutations have since demonstrated marked effects on the binding of neutralizing antibodies, attenuating the efficacy of mRNA vaccines. Since the variant’s initial emergence, several new Omicron subvariants have continued to emerge throughout the world, posing further challenges to current vaccination strategies. In particular, the XBB subvariant, which is a recombinant virus between BA.2.10.1.1 and BA.2.75.3.1.1.1, as well as the BA.2.3.20 and BR.2 subvariants that contain mutations distinct from BA.2 and BA.2.75, have been increasing in proportion of variants sequenced. Here we show that antibodies induced by 3-dose mRNA booster vaccination as well as BA.1 and BA.4/5 wave-infection effectively neutralize BA.2, BR.2, and BA.2.3.20, but had significantly reduced efficiency against XBB. This escape by XBB could be partially recovered by the administration of a bivalent booster mRNA vaccine. XBB also demonstrates modest increases in fusogenicity and spike processing relative to BA.2, though infectivity in both human lung epithelial cell line Calu-3 and HEK293T-ACE2 cells remains comparable to BA.2. Notably, the BA.2.3.20 subvariant exhibits enhanced infectivity in the lung-derived CaLu-3 cells and in 293T-ACE2 cells and increased fusogenicity and spike processing relative to BA.2. Overall, our results demonstrate that the XBB subvariant is highly neutralization resistant, and that newly emerged Omicron variants have altered fusogenicity and infectivity, highlighting the need for continued monitoring of the immune escape and tissue tropism of emerging Omicron subvariants.
Keywords: SARS-CoV-2, Neutralizing Antibody Resistance, XBB Variant