Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge
Abstract
Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identifymore »
- Authors:
-
- Robert Koch-Institut, Berlin (Germany)
- Paul-Ehrlich-Institut, Langen (Germany)
- Publication Date:
- OSTI Identifier:
- 22581669
- Resource Type:
- Journal Article
- Journal Name:
- Virology
- Additional Journal Information:
- Journal Volume: 489; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; AIDS VIRUS; ANIMALS; IMMUNITY; SAFETY; VACCINES; VIRAL DISEASES
Citation Formats
Gabriel, Benjamin, Fiebig, Uwe, Hohn, Oliver, Plesker, Roland, Coulibaly, Cheick, Cichutek, Klaus, Mühlebach, Michael D., Bannert, Norbert, Kurth, Reinhard, and Norley, Stephen. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge. United States: N. p., 2016.
Web. doi:10.1016/J.VIROL.2015.11.030.
Gabriel, Benjamin, Fiebig, Uwe, Hohn, Oliver, Plesker, Roland, Coulibaly, Cheick, Cichutek, Klaus, Mühlebach, Michael D., Bannert, Norbert, Kurth, Reinhard, & Norley, Stephen. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge. United States. https://doi.org/10.1016/J.VIROL.2015.11.030
Gabriel, Benjamin, Fiebig, Uwe, Hohn, Oliver, Plesker, Roland, Coulibaly, Cheick, Cichutek, Klaus, Mühlebach, Michael D., Bannert, Norbert, Kurth, Reinhard, and Norley, Stephen. 2016.
"Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge". United States. https://doi.org/10.1016/J.VIROL.2015.11.030.
@article{osti_22581669,
title = {Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge},
author = {Gabriel, Benjamin and Fiebig, Uwe and Hohn, Oliver and Plesker, Roland and Coulibaly, Cheick and Cichutek, Klaus and Mühlebach, Michael D. and Bannert, Norbert and Kurth, Reinhard and Norley, Stephen},
abstractNote = {Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.},
doi = {10.1016/J.VIROL.2015.11.030},
url = {https://www.osti.gov/biblio/22581669},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 489,
place = {United States},
year = {Mon Feb 15 00:00:00 EST 2016},
month = {Mon Feb 15 00:00:00 EST 2016}
}