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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Continued evasion of neutralizing antibody response by Omicron XBB.1.16
Julia N Faraone1, Panke Qu2, Yi-Min Zheng2
1Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the efficacy of vaccination efforts against coronavirus disease 2019 (COVID-19). The Omicron XBB lineage of SARS-CoV-2 has presented dramatic evasion of neutralizing antibodies stimulated by mRNA vaccination and COVID-19 convalescence. XBB.1.16, characterized by two mutations relative to the dominating variant XBB.1.5, i.e., E180V and K478R, has been on the rise globally. In this study, we compare the immune escape of XBB.1.16 with XBB.1.5, alongside ancestral variants D614G, BA.2, and BA.4/5. We demonstrate that XBB.1.16 is strongly immune evasive, with extent comparable to XBB.1.5 in bivalent-vaccinated healthcare worker sera, 3-dose-vaccinated healthcare worker sera, and BA.4/5-wave convalescent sera. Interestingly, the XBB.1.16 spike is less fusogenic than that of XBB.1.5, and this phenotype requires both E180V and K478R mutations to manifest. Overall, our findings emphasize the importance of the continued surveillance of variants and the need for updated mRNA vaccine formulations.
Insights
The Omicron XBB.1.16 variant shows significant immune evasion, similar to XBB.1.5, challenging COVID-19 vaccines. This highlights the need for ongoing variant surveillance and updated vaccine formulations.
Area of Science:
- Virology
- Immunology
- Epidemiology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution, particularly Omicron variants like XBB, poses challenges to vaccine efficacy.
- The Omicron XBB lineage exhibits substantial immune evasion against antibodies from mRNA vaccination and COVID-19 infection.
- The XBB.1.16 variant, with mutations E180V and K478R, is emerging globally and requires comparative analysis.
Purpose of the Study:
- To compare the immune escape properties of the SARS-CoV-2 XBB.1.16 variant against XBB.1.5 and earlier variants.
- To assess the fusogenicity of the XBB.1.16 spike protein in relation to XBB.1.5.
- To underscore the necessity for continuous monitoring of viral evolution and vaccine updates.
Main Methods:
- Comparative analysis of immune evasion using sera from bivalent-vaccinated and 3-dose-vaccinated healthcare workers.
- Evaluation of sera from individuals convalescent during the BA.4/5 wave.
- Assessment of spike protein fusogenicity linked to specific mutations.
Main Results:
- XBB.1.16 demonstrates strong immune evasion, comparable to XBB.1.5, across various vaccinated and convalescent human sera.
- The XBB.1.16 spike protein exhibits reduced fusogenicity compared to XBB.1.5.
- The diminished fusogenicity phenotype of XBB.1.16 is dependent on the presence of both E180V and K478R mutations.
Conclusions:
- The XBB.1.16 variant presents a significant immune escape threat, necessitating vigilance.
- Updated mRNA vaccine formulations may be required to address the immune evasion posed by emerging variants like XBB.1.16.
- Continuous surveillance of SARS-CoV-2 variants is crucial for public health strategies.
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