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  • Title: Humoral immune responses against minute virus of mice vectors.
    Author: Lang SI, Giese NA, Rommelaere J, Dinsart C, Cornelis JJ.
    Journal: J Gene Med; 2006 Sep; 8(9):1141-50. PubMed ID: 16800041.
    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.
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