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Inactivated and Immunogenic SARS-CoV-2 for Safe Use in Immunoassays and as an Immunization Control for Non-Clinical
Mariana Pierre de Barros Gomes1, José Henrique Rezende Linhares1, Tiago Pereira Dos Santos1
1Virological Technology Laboratory, Bio-Manguinhos/FIOCRUZ, Rio de Janeiro 21040-900, RJ, Brazil.
Viruses
|July 29, 2023
Summary
A novel inactivation method using beta-propiolactone effectively rendered SARS-CoV-2 safe for research. This inactivated virus maintains its structure and antigenicity, proving valuable for developing diagnostic tools and vaccines.
Area of Science:
- Virology
- Immunology
- Biotechnology
Background:
- Safe handling of SARS-CoV-2 is crucial for research and development.
- Whole, inactivated virus particles are valuable for assay development and immune response studies.
Purpose of the Study:
- To optimize a SARS-CoV-2 inactivation protocol for safe use in research.
- To confirm the integrity and antigenicity of the inactivated virus.
- To evaluate the efficacy of the inactivated virus in preclinical models.
Main Methods:
- Evaluation of multiple SARS-CoV-2 inactivation protocols, focusing on beta-propiolactone treatment.
- Confirmation of inactivation using cell-based assays and viral structure analysis (RT-qPCR, transmission electron microscopy).
- Assessment of antigenicity via ELISA and evaluation in a K18-hACE2 mouse model.
Main Results:
- 0.03% beta-propiolactone for 24 hours achieved >99.99% SARS-CoV-2 inactivation without cytopathic effects.
- Inactivated SARS-CoV-2 preserved RNA integrity and viral structure.
- Immunization with inactivated SARS-CoV-2 elicited high neutralizing antibody titers and improved survival in mice challenged with live virus.
Conclusions:
- Optimized beta-propiolactone treatment provides a reliable method for SARS-CoV-2 inactivation.
- The inactivated virus is suitable for developing diagnostic kits, antibody production, and non-clinical trials.
- Rigorous validation is essential to ensure viral inactivation and prevent contamination.

