Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.

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.

• Authors: Huanbin Xu, Anne-Marie 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
• Journal: EBioMedicine (EBioMedicine) Vol. 18 Pg. 204-215 (Apr 2017) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 28302457 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antigens, Heterophile
• SAIDS Vaccines

Topics

• Adenoviridae (genetics)
• Animals
• Antigens, Heterophile (genetics, immunology, metabolism)
• CD4-Positive T-Lymphocytes (cytology, immunology)
• CD8-Positive T-Lymphocytes (cytology, immunology)
• Genetic Vectors (genetics, immunology, metabolism)
• HEK293 Cells
• Humans
• Macaca mulatta
• Mice
• Retroviruses, Simian (physiology)
• SAIDS Vaccines (immunology)
• Viremia (immunology, prevention & control)
• Virus Replication (physiology)