Lymphoid activation: a confounding factor in AIDS vaccine development?
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.
Richardson
Jennifer
J
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Broche
Sophie
S
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Baud
Sandrine
S
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Leste-Lasserre
Thierry
T
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Féménia
Françoise
F
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Levy
Daniel
D
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Moraillon
Anne
A
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Pancino
Gianfranco
G
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
Sonigo
Pierre
P
Génétique des Virus, Institut Cochin (INSERM U567 CNRS UMR 8104), 22 rue Méchain, 75014 Paris, France1.
D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D016089:Immunodeficiency Virus, Feline / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*
D006023:Glycoproteins; D006514:Hepatitis B Surface Antigens; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C445079:envelope protein, Feline immunodeficiency virus