Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge

作者：Bogers Willy M J M^*; Davis David; Baak Ilona; Kan Elaine; Hofman Sam; Sun Yide; Mortier Daniella; Lian Ying; Oostermeijer Herman; Fagrouch Zahra; Dubbes Rob; van der Maas Martin; Mooij Petra; Koopman Gerrit; Verschoor Ernst; Langedijk Johannes P M; Zhao Jun; Brocca Cofano Egidio; Robert Guroff Marjorie; Srivastava Indresh; Barnett Susan; Heeney Jonathan L

来源：Virology, 2008, 382(2): 217-225.

DOI：10.1016/j.virol.2008.09.016

• HIV vaccine
• Animal model
• Mucosal challenge
• Nabs
• ADCC

Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-1(89.6p) env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infections doses of the CCR5 tropic SHIV(SF162p4). Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody-dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor-F-cell responses, but rather with the Nab titer prior to exposure.

• 出版日期2008-12-20