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Development of COVID-19 Vaccine Candidates Using Attenuated Recombinant Vesicular Stomatitis Virus Vectors with M Protein Mutations
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Development of COVID-19 Vaccine Candidates Using Attenuated Recombinant Vesicular Stomatitis Virus Vectors with M Protein Mutations
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Journal Article
Development of COVID-19 Vaccine Candidates Using Attenuated Recombinant Vesicular Stomatitis Virus Vectors with M Protein Mutations
2025
Overview
Recombinant vesicular stomatitis virus (rVSV) is a promising viral vaccine vector for addressing the COVID-19 pandemic. Inducing mucosal immunity via the intranasal route is an ideal strategy for rVSV-based vaccines, but it requires extremely stringent safety standards. In this study, we constructed two rVSV variants with amino acid mutations in their M protein: rVSV-M2 with M33A/M51R mutations and rVSV-M4 with M33A/M51R/V221F/S226R mutations, and developed COVID-19 vaccines based on these attenuated vectors. By comparing viral replication capacity, intranasal immunization, intracranial injection, and blood cell counts, we demonstrated that the M protein mutation variants exhibit significant attenuation effects both in vitro and in vivo. Moreover, preliminary investigations into the mechanisms of virus attenuation revealed that these attenuated viruses can induce a stronger type I interferon response while reducing inflammation compared to the wild-type rVSV. We developed three candidate vaccines against SARS-CoV-2 using the wildtype VSV backbone with either wild-type M (rVSV-JN.1) and two M mutant variants (rVSV-M2-JN.1 and rVSV-M4-JN.1). Our results confirmed that rVSV-M2-JN.1 and rVSV-M4-JN.1 retain strong immunogenicity while enhancing safety in hamsters. In summary, the rVSV variants with M protein mutations represent promising candidate vectors for mucosal vaccines and warrant further investigation.
Publisher
MDPI AG,MDPI
Subject
/ Animals
/ Antibodies, Viral - immunology
/ COVID-19 - prevention & control
/ COVID-19 Vaccines - administration & dosage
/ COVID-19 Vaccines - genetics
/ COVID-19 Vaccines - immunology
/ Female
/ Humans
/ Mice
/ Mutation
/ Plasmids
/ Proteins
/ Severe acute respiratory syndrome coronavirus 2
/ Vaccines, Attenuated - administration & dosage
/ Vaccines, Attenuated - genetics
/ Vaccines, Attenuated - immunology
/ Vaccines, Synthetic - immunology
/ Vesicular stomatitis Indiana virus - genetics
/ Viral Matrix Proteins - genetics
/ Viral Matrix Proteins - immunology
/ Viruses
