4613347705

WT VSV and the Mmsir mutant are actively being developed for clinical oncolytic applications (Diaz et al., 2007; Nguyen et al., 2008). For obvious safety reasons, virus replication has to be limited both in space and time, which restricts virus availability for oncolysis. For VSV, this is achieved through the rapid generation of neutralizing antibodies. Thus, we compared the kinetics of neutralizing antibody development against each mutant (Fig. Ib). Total VSV-specific neutralizing immunoglobulins (mainly composed of IgMs in the first few days) were detectable for all VSV strains by day 4 foliowing the first VSV injection correlating with viral clearance kinetics. Class switching to neutralizing IgGs occurred by day 8. Of notę, neutralizing IgGs were detected as early as day 4 after Gór treatment. The neutralizing antibody response reached its maximum level between 8 and 12 days post-infection. Gór and WT VSV induced the strongest and fastest humoral response, followed by Gó, while the matrix mutant Mmsir generated a weaker humoral response. Since no virus could be detected for any viral strain neither in the tumor nor the spleen 4 days after the last injection, we conclude that the anti-MM5iR neutralizing antibody response was

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