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Animal: RNA Viruses |
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1
Immunopathologie Cellulaire et Moléculaire, Institut National de la Recherche Agronomique (INRA)2 and UMR INRA ENVA AFSSA 1161 de Virologie, Ecole Nationale Vétérinaire d’Alfort (ENVA)3, Maisons-Alfort, France
Author for correspondence: Pierre Sonigo. Fax +33 1 40 51 64 30. e-mail sonigo{at}cochin.inserm.fr
In a previous vaccination trial, inoculation of env gene DNA failed to elicit a detectable antibody response, yet accelerated virus dissemination in most immunized cats following challenge with feline immunodeficiency virus. This result raised the possibility that cell-mediated immune responses had given rise to immune-mediated enhancement of infection. Since high-level replication of immunodeficiency viruses in lymphocytes requires cellular activation, antigen-specific responses or non-specific polyclonal activation may have increased the frequency of optimal target cells. In the present DNA vaccination trial, although designed so as to minimize non-specific polyclonal activation, immune-mediated enhancement was nonetheless observed in certain immunized cats. Moreover, rapid virus dissemination in vivo was associated with the presence of T-helper responses prior to challenge, and was linked to increased susceptibility of lymphocytes to ex vivo infection. Immune activation may thus be a confounding factor in vaccination against lentivirus infection, diminishing vaccine efficacy and giving rise to immune-mediated enhancement.
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