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Lymphoid activation: a confounding factor in AIDS vaccine development?

Jennifer Richardson1, Sophie Broche1, Sandrine Baud1

  • 1Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.

The Journal of General Virology
|September 19, 2002
PubMed
Summary

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DNA vaccination against feline immunodeficiency virus (FIV) did not produce antibodies but enhanced virus spread. Immune activation, particularly T-helper responses, increased susceptibility to infection and diminished vaccine efficacy.

Area of Science:

  • Veterinary Immunology
  • Virology
  • Vaccine Development

Background:

  • Previous DNA vaccination trials with the env gene of feline immunodeficiency virus (FIV) failed to induce detectable antibody responses.
  • These trials paradoxically resulted in accelerated virus dissemination post-challenge in most immunized cats.

Purpose of the Study:

  • To investigate the role of immune-mediated enhancement in FIV DNA vaccination.
  • To explore the impact of immune activation on lentivirus vaccine efficacy.

Main Methods:

  • A DNA vaccination trial in cats using an FIV env gene construct.
  • Monitoring for antibody responses, virus dissemination, and cell-mediated immune responses (T-helper responses).
  • Assessing lymphocyte susceptibility to ex vivo infection.

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Main Results:

  • Immune-mediated enhancement of infection was observed in some cats despite efforts to minimize non-specific polyclonal activation.
  • Rapid virus dissemination in vivo correlated with pre-challenge T-helper responses.
  • Lymphocytes from immunized cats showed increased susceptibility to ex vivo infection.

Conclusions:

  • Immune activation, specifically T-helper responses, can be a confounding factor in lentivirus vaccination.
  • Immune activation may diminish vaccine efficacy and lead to immune-mediated enhancement of infection.
  • Further research is needed to understand and mitigate immune activation in lentivirus vaccine strategies.