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Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication

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Huanbin Xu, Anne-Marie Carola Andersson, Emeline Ragonnaud, Ditte Boilesen, Anders Tolver, Benjamin Anderschou Holbech Jensen, James L Blanchard, Alfredo Nicosia, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Allan Randrup Thomsen, Jan Pravsgaard Christensen, Ronald S. Veazey, Peter Johannes Holst

Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia.

Original languageEnglish
JournalEBioMedicine
Volume18
Pages (from-to)204–215
Number of pages12
ISSN2352-3964
DOIs
Publication statusPublished - Apr 2017

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