Impact of vaccine-induced mucosal high-avidity CD8+CTLs in delay of AIDS viral dissemination from mucosa

IM Belyakov, VA Kuznetsov, B Kelsall, D Klinman… - Blood, 2006 - ashpublications.org
IM Belyakov, VA Kuznetsov, B Kelsall, D Klinman, M Moniuszko, M Lemon, PD Markham…
Blood, 2006ashpublications.org
Natural HIV transmission occurs through mucosa, but it is debated whether mucosal
cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal
site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral
transmission is unknown. To address these questions, we used delay in acute-phase peak
viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a
peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can …
Abstract
Natural HIV transmission occurs through mucosa, but it is debated whether mucosal cytotoxic T lymphocytes (CTLs) can prevent or reduce dissemination from the initial mucosal site to the systemic circulation. Also, the role of CTL avidity in mucosal AIDS viral transmission is unknown. To address these questions, we used delay in acute-phase peak viremia after intrarectal challenge as an indicator of systemic dissemination. We found that a peptide-prime/poxviral boost vaccine inducing high levels of high-avidity mucosal CTLs can have an impact on dissemination of intrarectally administered pathogenic SHIV-ku2 in macaques and that such protection correlates better with mucosal than with systemic CTLs and particularly with levels of high-avidity mucosal CTLs.
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