Dataset Information

Attenuation of the M gene in Vesicular Stomatitis Virus Vector

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE296553 | GEO | 2025/09/03

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Mucosal immunity plays a pivotal role in providing comprehensive protection against upper-airway infections and effectively limiting the shedding and transmission of SARS-CoV-2. Despite its critical importance, there remains a notable absence of nasal spray vaccines endorsed for global use by the World Health Organization. This could be due to the inability of current intranasal vaccines to induce strong mucosal and systemic responses in humans, thus urgently entailing a next-generation of intranasal COVID-19 vaccines with novel and safe technologies. In this study, we prepared a two-component intranasal vaccine that combines adenovirus vectors with a self-assembled subunit protein. Specifically, the adenovirus vector expresses the spike protein of XBB.1.5 variant (Ad5XBB.1.5), and were mixed with the recombinant protein that developed derived from the receptor binding domain (RBD) of XBB.1.5 (RBDXBB.1.5-HR). Combination of Ad5XBB.1.5 and RBDXBB.1.5-HR elicited superior humoral and cellular immunity against XBB.1.5-included variants compared with the individual components. Importantly, the STING signaling pathway was found to be crucial for the adjuvant effect of the adenovirus vector. In addition, to increase the broad-spectrum neutralizing capacities, a trimeric protein derived from the BA.5 variant (RBDBA.5-HR) was incorporated to formulate a three-component vaccine (Ad5XBB.1.5+RBDXBB.1.5-HR+RBDBA.5-HR), indicating the utilization of a combination of an adenovirus-vectored and subunit protein vaccines has the potential to serve as a next-generation intranasal vaccine platform. Of note, intranasally delivery of two-component vaccine provided protective immunity against live Omicron XBB.1.16 virus challenge in mice. Furthermore, the combination of adenovirus and subunit protein vaccine demonstrates excellent tolerability and safety in human subjects, and is able to induce enhanced mucosal immunity as well as high levels of sera neutralizing antibody in all participants. These findings underscore its suitability for clinical application in the prevention of SARS-CoV-2 variants encompassing XBB lineages.

Dataset Information

Attenuation of the M gene in Vesicular Stomatitis Virus Vector

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets