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Lymphoid activation: a confounding factor in AIDS vaccine development?

Jennifer Richardson·Sophie Broche·Sandrine Baud·Thierry Leste-Lasserre·Françoise Féménia·Daniel Levy·Anne Moraillon·Gianfranco Pancino·Pierre Sonigo
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Abstract

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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AnimalsCatsCells, CulturedFeline Acquired Immunodeficiency SyndromeGlycoproteinsHepatitis B Surface AntigensHepatitis B virusImmunodeficiency Virus, FelineLeukocytes, MononuclearLymph NodesViral Envelope ProteinsViral LoadViral VaccinesJournal ArticleResearch Support, Non-U.S. Gov't

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Jennifer Richardson, Sophie Broche, Sandrine Baud, Thierry Leste-Lasserre, Françoise Féménia, Daniel Levy, Anne Moraillon, Gianfranco Pancino, Pierre Sonigo. 2002. Lymphoid activation: a confounding factor in AIDS vaccine development?. https://doi.org/10.1099/0022-1317-83-10-2515

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