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Vesiculovirus neutralization by natural IgM and complement.

Mulu Z Tesfay1, Arun Ammayappan, Mark J Federspiel

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|March 21, 2014
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Vesicular stomatitis virus (VSV) shows potential for cancer therapy but is neutralized by human serum. Replacing its G gene with Maraba virus

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Area of Science:

  • Virology
  • Oncology
  • Immunology

Background:

  • Vesicular stomatitis virus (VSV) is a promising oncolytic agent for cancer therapy.
  • VSV is rapidly neutralized by non-immune human serum, limiting its systemic application.
  • Maraba virus (MARV) exhibits resistance to human serum neutralization.

Purpose of the Study:

  • To engineer a VSV variant resistant to human serum neutralization for improved oncolytic virotherapy.
  • To evaluate the efficacy and safety of MARV-pseudotyped VSV in preclinical models.

Main Methods:

  • Recombinant VSV was generated by replacing the VSV G gene with the MARV G gene.
  • The host range and replication kinetics of the engineered VSV were compared to the parental VSV.
  • Neutralization susceptibility of the engineered VSV to non-immune human serum was assessed.

Main Results:

  • The engineered VSV (VSV-MARV-G) retained similar host range and replication kinetics to wild-type VSV.
  • VSV-MARV-G demonstrated significant resistance to neutralization by non-immune human serum.
  • This resistance is attributed to the MARV G protein's distinct antigenic properties.

Conclusions:

  • VSV pseudotyped with MARV G protein is resistant to human serum neutralization.
  • This engineered VSV is a potential candidate for systemic oncolytic virotherapy.
  • Further investigation is warranted for its application in treating disseminated cancers.