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Attenuation of the M gene in Vesicular Stomatitis Virus Vector

ABSTRACT: Attenuation of the M gene in Vesicular Stomatitis Virus Vector

PROVIDER: PRJNA1259969 | ENA |

REPOSITORIES: ENA

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Attenuation of the M gene in Vesicular Stomatitis Virus Vector

Project description: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 wild-type rVSV (rVSV-JN.1) and the two 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.

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Project description:We advanced a promising experimental vaccine for immunizing against the Lassa virus surface glycoprotein as a candidate for human trials. Preclinical evaluation of the vaccine candidate based on a live vesicular stomatitis virus (VSV) vector showed that it was highly efficacious in cynomolgus macaques consistent with earlier research studies, and that the animals developed serum antibodies that could mediate antiviral effector functions including direct neutralization of virus infectivity. As part of this evaluation, we analyzed whole-blood transcriptomes from each study subject prior to vaccination and at 1 day and 3 days post-vaccination.

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Project description:Vesicular stomatitis virus strain:Mudd-Summer Indiana Raw sequence reads

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Analysis of global gene expression profiles of hPAF1 deficient A549 cells during infection with H1N1 influenza A virus or vesicular stomatitis virus (VSV)

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Analysis of global gene expression profiles of hPAF1 deficient A549 cells during infection with H1N1 influenza A virus or vesicular stomatitis virus (VSV)

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