Humoral immune responses against minute virus of mice vectors

✍ Scribed by Susanne I. Lang; Nathalia A. Giese; Jean Rommelaere; Christiane Dinsart; Jan J. Cornelis

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 200 KB
• Volume: 8
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.940

✦ Synopsis

Abstract

Background

Owing to their oncolytic properties, autonomous rodent parvoviruses and derived vectors constitute potential anti‐tumor agents.

Methods

Humoral immune responses to minute virus of mice (MVMp) were characterized. In particular, the generation of neutralizing antibodies on subsequent therapeutic virus applications was evaluated in a mouse melanoma model. Mice bearing subcutaneous melanomas were injected intratumorally with virus and re‐injected 10 days later in a second tumor on the other flank. Four days after the first or second injection, the tumors and lymph nodes were analyzed by RT‐PCR for gene expression.

Results

Injection of MVMp in tumor‐bearing B6 mice resulted in viral gene expression in tumors and draining lymph nodes. A repeated virus administration did not lead to detectable viral transcription if it was preceded by a virus infection 10 days earlier. This protection correlated with the induction of virus‐neutralizing antibodies following the first virus application. The restrictions on viral gene expression after a consecutive MVMp injection could be alleviated in subsequent applications by the use of viruses consisting of MVMp genomes packaged into capsids of a related parvovirus. Neutralizing antibody induction was irrespective of the route of administration and of the presence of a tumor and persisted at significant levels at least up to 26 weeks after the viral infection. MVMp infection of B6 mice stimulated the generation of IgM and IgG anti‐viral antibodies, the latter mainly of the T‐helper (Th) 1‐dependent IgG2, and the T‐cell‐independent IgG3 subclasses.

Conclusions

Neutralizing antibodies impede the effectiveness of a subsequent virus administration, but can be overcome by pseudotyping. Copyright © 2006 John Wiley & Sons, Ltd.