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Vaccination to prevent persistent viral infection

M B Oldstone1, A Tishon, M Eddleston

  • 1Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.

Journal of Virology
|July 1, 1993
PubMed
Summary

A novel vaccine inducing cytotoxic T lymphocytes (CTL) prevents persistent viral infections by targeting viral epitopes. This CTL-inducing vaccine offers complete protection against immunosuppressive viruses, demonstrating a feasible "string of CTL epitopes" vaccination strategy.

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Area of Science:

  • Immunology
  • Virology
  • Vaccinology

Background:

  • Persistent viral infections cause significant human morbidity and mortality.
  • Viruses establish persistence by evading host immune responses, particularly cytotoxic T lymphocytes (CTL).
  • Some viruses suppress the host CTL response to establish persistent infections.

Purpose of the Study:

  • To investigate a vaccine strategy for preventing persistent viral infections.
  • To determine if inducing CTL responses can confer protection against a virus that suppresses CTL.
  • To explore the feasibility of a "string of CTL epitopes" vaccine.

Main Methods:

  • Developed a vaccine designed to induce CTL responses, independent of antiviral antibodies.
  • Administered the vaccine prior to viral challenge in a mouse model.

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  • Assessed viral persistence in various tissues, including lymphocytes and macrophages.
  • Tested vaccines incorporating single or multiple CTL epitopes for different MHC haplotypes.

    • Main Results:

    • Vaccination inducing CTL conferred complete protection against viral persistence in all analyzed tissues.
    • Vaccine efficacy was demonstrated even with minimal viral peptide sequences (10 amino acids) representing CTL epitopes.
    • A single vaccine containing two distinct CTL epitopes protected against viral challenge in mice with different MHC haplotypes.
    • The CTL vaccine protected against the establishment of persistence by an immunosuppressive virus.

    Conclusions:

    • Vaccination strategies focused on inducing CTL responses are effective in preventing persistent viral infections.
    • A "string of CTL epitopes" vaccine approach is feasible and can provide broad protection.
    • Targeting CTL responses is a viable strategy against viruses that employ immune evasion tactics, including immunosuppression.