The reassessed potential of SARS-CoV-2 attenuation for COVID-19 vaccine development: a systematic review

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Virus. May 7, 2022; 14 (5): 991. doi: 10.3390 / v14050991.

SUMMARY

Live attenuated SARS-CoV-2 vaccines received relatively little attention during the COVID-19 pandemic. However, several methods are known to obtain attenuated coronaviruses. In this systematic review, coronavirus attenuation strategies were identified, which could potentially be applied to SARS-CoV-2. PubMed, Scopus, Web of Science, and Embase databases were searched to identify relevant articles describing attenuated mutations tested in vivo. In the case of coronaviruses other than SARS-CoV-2, sequence alignment was used to rule out attenuating mutations that cannot be applied to SARS-CoV-2. The possible immunogenicity, safety, and efficacy of the attenuated SARS-CoV-2 vaccine from animal study data were discussed. A total of 27 attenuation strategies, used to create 101 different coronaviruses, have been described in 56 eligible articles. Disruption of the furin cleavage site in the SARS-CoV-2 ear protein was identified as the most promising strategy. Replacing basic sequences of transcriptional regulatory signals, which prevents recombination with wild-type viruses, also seems especially advantageous. Other important attenuating mutations mainly included the prevention of innate immunity evasion. Sufficiently attenuated coronaviruses usually did not cause any significant disease in susceptible animals and protected them from virulent virus challenges. This indicates that attenuated COVID-19 vaccines can be considered a potential strategy to combat the SARS-CoV-2 threat.

PMID: 35632736 | DOI: 10.3390 / v14050991

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