Exploring immune evasion of SARS-CoV-2 variants using a pseudotyped system.

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• Coronavirus disease 2019 (COVID-19) cases in the US have been dominated by the SARS-CoV-2 XBB.1.5 variant since late 2022.
• Understanding the immune evasion properties of circulating SARS-CoV-2 variants is crucial for public health.

Purpose of the Study:

• To develop and validate a pseudovirus (PsV) system for studying SARS-CoV-2 variant infections in a Biosafety Level 2 (BSL-2) laboratory.
• To assess the immune evasion capabilities of various SARS-CoV-2 PsV variants, including XBB.1.5, using neutralization assays.

Main Methods:

• A lentiviral vector system was engineered with ZsGreen1 and Firefly luciferase (Fluc) dual reporter genes for PsV production.
• A panel of SARS-CoV-2 PsV variants (prototype, Delta, BA.5, XBB.1, XBB.1.5) was created.
• A HEK-293T cell line expressing human ACE2 was utilized for infection studies.
• Neutralization assays were performed using serum from rats immunized with a PF-D-Trimer protein vaccine.

Main Results:

• The developed PsV system successfully models different SARS-CoV-2 variants.
• The XBB variant, particularly XBB.1.5, demonstrated significantly stronger immune evasion compared to prototype, Delta, and BA.5 PsV variants.
• The study validated the utility of PsV variants in neutralization assays.

Conclusions:

• The pseudovirus system provides a robust platform for investigating SARS-CoV-2 variant infectivity and immune response.
• The findings highlight the enhanced immune evasion of the XBB.1.5 variant, underscoring the need for updated vaccines or therapeutics.
• This neutralization assay approach can predict the efficacy of interventions against future SARS-CoV-2 variants.