The viral vector vaccine VSV-GP boosts immune response upon repeated applications

Poster presentation AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 2012

Background: Vesicular stomatitis virus (VSV) is a potent candidate vaccine vector for various viral diseases (e.g. HIV, HCV, RSV). The biggest
Poster presentation AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 2012

Background: Vesicular stomatitis virus (VSV) is a potent candidate vaccine vector for various viral diseases (e.g. HIV, HCV, RSV). The biggest limitation of VSV, however, is its neurotoxicity, which limits application in humans. The second drawback is that VSV induces neutralizing antibodies rapidly and is thus ineffective as a vaccine vector upon repeated applications. Our group has recently shown that VSV pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV), VSV-GP, is not neurotoxic. The aim of this project was to evaluate the potential of VSV-GP as a vaccine vector.

Methods: For this purpose, we used Ovalbumin (OVA) as a model antigen and analyzed immunogenicity of GP-pseudotyped and wildtype VSV containing OVA (VSV-GP-OVA and VSV-OVA) in vitro and in vivo in mouse models.

Results: We showed that both vectors infected murine bone marrow-derived dendritic cells (bmDCs) in vitro. These bmDCs were able to activate OVA specific CD8+ and CD4+ T cells. Immunization experiments in mice revealed that both VSV-OVA and VSV-GP-OVA induced functional OVA-specific cytotoxic T cells (CTLs) after a single immunization. In addition, with both viruses, mice generated antibodies against OVA. However, boosting with the same virus was only possible for the GP-pseudotyped virus but not for wild type VSV. The efficacy of repeated immunization with VSV-OVA was most likely limited by high levels of neutralizing antibodies, which we detected after the first immunization. In contrast, no neutralizing antibodies against VSV-GP were induced even after boosting.

Conclusion: Taken together, we showed that the non-neurotoxic VSV-GP is able to induce specific T cell and B cell responses against the model antigen OVA to the same level as the wild type VSV vector. However, in contrast to wild type VSV, VSV-GP-OVA boosted the immune response upon repeated applications. Thus, VSV-GP is a promising novel vaccine vector. 
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Metadaten
Author:Reinhard Tober, Zoltan Banki, Asim Ejaz, Alex Muik, Lisa Mareike Egerer, Dorothee von Laer, Janine Kimpel
URN:urn:nbn:de:hebis:30:3-264121
DOI:http://dx.doi.org/10.1186/1742-4690-9-S2-P301
ISSN:1742-4690
Parent Title (English):Retrovirology
Publisher: BioMed Central
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2012/09/13
Date of first Publication:2012/09/13
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/09/21
Volume:9
Issue:9(Suppl 2):P301
Pagenumber:1
First Page:1
Last Page:1
Note:
© 2012 Tober et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Medizin
Georg-Speyer-Haus
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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