Humoral immune responses against minute virus of mice vectors.
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.
Lang
Susanne I
SI
Deutsches Krebsforschungszentrum, Applied Tumor Virology Program, Abteilung F010, Heidelberg, Germany.. Lang.Susanne@mayo.edu
Giese
Nathalia A
NA
Rommelaere
Jean
J
Dinsart
Christiane
C
Cornelis
Jan J
JJ
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005814:Genes, Viral; D015316:Genetic Therapy; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008915:Minute Virus of Mice / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D009500:Neutralization Tests; D019065:Virus Assembly
D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M