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Immunization by Replication-Competent Controlled Herpesvirus Vectors.

David C Bloom1, Robert K Tran1, Joyce Feller1

  • 1Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.

Journal of Virology
|June 15, 2018
PubMed
Summary
This summary is machine-generated.

Controlled herpes simplex virus vectors, activated by heat and antiprogestin, showed enhanced immunogenicity in mice. Localized, limited replication of these vectors significantly boosted immune responses against the virus and heterologous antigens.

Keywords:
herpesvirus vectorimmunizationregulation of viral genesregulation of viral replicationtwo-component gene switchvaccination

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Area of Science:

  • Virology
  • Immunology
  • Vaccine Development

Background:

  • Replication-competent viruses are typically attenuated or inactivated for vaccine use.
  • Controlling viral replication is key to balancing safety and immunogenicity.

Purpose of the Study:

  • To develop replication-controlled herpes simplex virus vectors (HSV-1) for enhanced immunogenicity.
  • To investigate if controlled, localized viral replication improves immune responses to viral or heterologous antigens.

Main Methods:

  • Derived replication-competent HSV-1 vectors with replication-essential genes under a heat/antiprogestin-controlled gene switch.
  • Administered vectors to mice, activating replication locally with heat and antiprogestin.
  • Assessed immunogenicity using lethal challenge models and measured antibody/cellular immune responses.

Main Results:

  • Unactivated vectors provided some protection; single localized activation significantly enhanced immune responses and protection.
  • Activated vectors induced superior neutralizing antibody and HSV-1-specific cellular immunity compared to unactivated vectors.
  • A vector expressing equine influenza virus hemagglutinin showed enhanced antigen-specific immune responses upon activation.

Conclusions:

  • Localized, transient activation of replication-competent herpesvirus vectors greatly enhances immune responses.
  • This approach offers a promising strategy for developing novel vaccines, especially for difficult-to-vaccinate populations.
  • Controlled viral replication, rather than attenuation, may be critical for potent and balanced immunity.