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Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication
- Source :
- EBioMedicine, Vol 18, Iss C, Pp 204-215 (2017)
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 18
- Issue :
- C
- Database :
- Directory of Open Access Journals
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.682d37b8db4cfeb554f35e480eb8f5
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.ebiom.2017.03.003