Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

• DOI: 10.1084/jem.20081524
• Publication Date: 2008-10-07T00:45:09Z
• Authors: Matthew R. Reynolds; Andrea M. Weiler; Kim L. Weisgrau; Shari M. Piaskowski; Jessica R. Furlott; Jason T. Weinfurter; Masahiko Kaizu; Taeko Soma; Enrique J. León; Caitlin MacNair; Dan P. Leaman; Michael B. Zwick; Emma Gostick; Solomon K. Musani; David A. Price; Thomas C. Friedrich; Eva G. Rakasz; Nancy A. Wilson; Adrian B. McDermott; Rosanne Boyle; David B. Allison; Dennis R. Burton; Wayne C. Koff; David I. Watkins
• Keywords: Heterologous; Simian immunodeficiency virus; Attenuated vaccine

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) and challenged with highly pathogenic heterologous isolate. Vaccinees reduced viral replication by ∼2 logs between weeks 2–32 (P ≤ 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated control completely suppressed acute phase the challenge virus, implicating CD8+ T cells control. Furthermore, transient depletion peripheral lymphocytes four during chronic resulted an increase replication. In two these animals, recrudescent population contained only strain not virus. Alarmingly, however, found evidence recombinant viruses emerging some vaccinated animals. This finding argues strongly attenuated as solution epidemic. On more positive note, our results suggest that MHC-I–restricted contribute protection induced SIV demonstrate vaccine-induced cell responses can viruses.