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Evaluating replication-defective vesicular stomatitis virus as a vaccine vehicle
Ayaz M Majid1, Heather Ezelle, Sangeeta Shah
1Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33136, USA.
Journal of Virology
|July 1, 2006
Summary
New vesicular stomatitis virus (VSV) vectors expressing hepatitis C virus (HCV) proteins elicit robust immune responses in mice. These engineered viruses show promise for developing effective HCV vaccines and immunotherapies.
Area of Science:
- Virology and Immunology
- Vaccine Development
- Hepatitis C Virus (HCV) Research
Background:
- Hepatitis C virus (HCV) infection poses a significant global health challenge.
- Development of effective vaccines and immunotherapies against HCV is crucial.
- Vesicular stomatitis virus (VSV) is a potential platform for vaccine delivery.
Purpose of the Study:
- To generate and characterize replication-competent and nonpropagating VSV vectors expressing HCV structural proteins (core, E1, E2).
- To evaluate the immunogenicity of these VSV-HCV vectors in murine models.
- To assess the potential of these vectors for vaccine and immunotherapy applications against HCV.
Main Methods:
- Generation of replication-competent (VSV-C/E1/E2) and replication-defective (VSVDeltaG-C/E1/E2) VSV vectors.
- Expression and characterization of HCV structural proteins within the VSV vectors.
- Immunization of BALB/c mice via intravenous or intraperitoneal routes.
- Assessment of antibody responses and T-cell activity (IFN-gamma production) using ELISPOT assays.
- Evaluation of protection against HCV E2-expressing tumors and challenge with recombinant vaccinia virus.
Main Results:
- VSV-C/E1/E2 and VSVDeltaG-C/E1/E2 successfully expressed high levels of authentic HCV core, E1, and E2 proteins.
- Immunization induced significant and comparable HCV core and E2 antibody responses, as well as HCV-specific CD8(+) T-cell activity.
- Mice immunized with VSVDeltaG-C/E1/E2 showed protection against HCV E2-expressing tumors and enhanced anti-tumor T-cell responses.
- Pre-immunization with VSV-HCV vectors reduced the replication of a challenge recombinant vaccinia virus expressing HCV proteins.
Conclusions:
- Replication-defective VSV can be engineered to express high levels of antigenically authentic HCV glycoproteins.
- VSV-HCV vectors are immunogenic, inducing both humoral and cellular immune responses against HCV proteins.
- This VSV-based strategy holds promise for the development of effective vaccines and immunotherapies for HCV-related diseases.
