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A lentiviral vector pseudotype suitable for vaccine development.

Luciene Lopes1, Marie Dewannieux, Yasuhiro Takeuchi

  • 1Immunity and Infection, University College London, London, UK.

The Journal of Gene Medicine
|March 12, 2011
PubMed
Summary
This summary is machine-generated.

The Ross River virus (RRV) envelope is a viable alternative for lentiviral vector (LV) vaccine production, enabling in vitro and in vivo studies. While requiring higher doses, RRV-LV offers improved production potential for future clinical applications.

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Area of Science:

  • * Virology and Immunology
  • * Gene Therapy and Vaccine Development

Background:

  • * Lentiviral vectors (LV) show promise as vaccines due to their ability to transduce dendritic cells (DC) in vivo.
  • * Clinical translation of LV vaccines necessitates efficient bulk production methods.
  • * The commonly used vesicular stomatitis virus envelope (VSV-G) presents cytotoxicity challenges for stable LV production.

Purpose of the Study:

  • * To identify a suitable envelope for the large-scale production of lentiviral vector (LV) vaccines.
  • * To evaluate the efficacy of the Ross River virus (RRV) envelope as an alternative to the cytotoxic VSV-G envelope for LV production.
  • * To assess the potential of RRV-enveloped LV for preclinical and clinical applications.

Main Methods:

  • * Selection and utilization of the Ross River virus (RRV) envelope for lentiviral vector (LV) pseudotyping.
  • * Comparative analysis of RRV-enveloped LV (RRV-LV) and VSV-G-enveloped LV (VSV-G-LV) infectivity in mouse and human cell lines (293T and 3T3).
  • * Titration of LV vectors and assessment of T cell responses in immunized mice and human myeloid dendritic cells (mDC).

Main Results:

  • * RRV-pseudotyped LV (RRV-LV) demonstrated infectivity towards mouse myeloid dendritic cells (mDC) in vitro and successfully immunized mice.
  • * A significantly higher dose (approximately 50-fold) of RRV-LV was required to elicit a T cell response comparable to VSV-G-LV.
  • * RRV-LV proved capable of infecting human mDC and priming a human T cell immune response.

Conclusions:

  • * The RRV envelope is a promising candidate for developing stable lentiviral vector (LV) producer cell lines.
  • * RRV-enveloped LV vaccines are suitable for testing in both murine models and human immune cell cultures.
  • * Despite requiring higher doses, the production advantages of RRV-LV may offset this for vaccine efficacy, facilitating further development.