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Updated: Aug 7, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Humoral immune responses against minute virus of mice vectors
Susanne I Lang1, Nathalia A Giese, Jean Rommelaere
1Deutsches Krebsforschungszentrum, Applied Tumor Virology Program, Abteilung F010, Heidelberg, Germany.. Lang.Susanne@mayo.edu
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.
Insights
Rodent parvoviruses show anti-tumor potential. However, neutralizing antibodies generated after initial MVMp virus therapy can block repeat treatments, a challenge overcome by pseudotyping viral vectors.
Area of Science:
- Oncolytic virotherapy
- Immunology
Background:
- Autonomous rodent parvoviruses possess oncolytic properties, making them promising candidates for anti-tumor therapies.
- Minute virus of mice (MVMp) is a type of parvovirus explored for its therapeutic potential.
Purpose of the Study:
- To characterize humoral immune responses to MVMp, focusing on neutralizing antibody generation after therapeutic virus administration.
- To evaluate the impact of these antibodies on subsequent MVMp treatments in a preclinical cancer model.
Main Methods:
- Mice with melanomas received intratumoral MVMp injections, with a second injection in a contralateral tumor 10 days later.
- Tumors and lymph nodes were analyzed for viral gene expression using RT-PCR.
- Humoral immune responses, including antibody subclasses, were assessed.
Main Results:
- MVMp administration led to viral gene expression in tumors and draining lymph nodes.
- Prior MVMp infection induced neutralizing antibodies that prevented viral transcription upon re-administration.
- Pseudotyping MVMp with related parvovirus capsids restored viral gene expression in subsequent applications.
- Neutralizing antibodies persisted for at least 26 weeks and included IgG2 and IgG3 subclasses.
Conclusions:
- Neutralizing antibodies generated against MVMp limit the efficacy of repeated oncolytic virus therapy.
- Pseudotyping viral vectors offers a strategy to circumvent pre-existing neutralizing immunity and enhance therapeutic outcomes.
