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Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus

BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV) challenge. The mechanisms responsible for the loss of protection remain to be defined. The...

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Autores principales: Genescà, Meritxell, McChesney, Michael B., Miller, Christopher J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843738/
https://www.ncbi.nlm.nih.gov/pubmed/20352116
http://dx.doi.org/10.1371/journal.pone.0009814
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author Genescà, Meritxell
McChesney, Michael B.
Miller, Christopher J.
author_facet Genescà, Meritxell
McChesney, Michael B.
Miller, Christopher J.
author_sort Genescà, Meritxell
collection PubMed
description BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV) challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera® administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera®, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera® SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-γ production were similar, the SIV-specific CD8(+) T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+) T cells from untreated animals. CONCLUSIONS: Depo-Provera® did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera® on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results demonstrate that the effects of hormonal contraceptives on vaccine efficacy need to be considered in the context of testing and use of an AIDS vaccine.
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spelling pubmed-28437382010-03-27 Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus Genescà, Meritxell McChesney, Michael B. Miller, Christopher J. PLoS One Research Article BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV) challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera® administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera®, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera® SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-γ production were similar, the SIV-specific CD8(+) T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+) T cells from untreated animals. CONCLUSIONS: Depo-Provera® did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera® on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results demonstrate that the effects of hormonal contraceptives on vaccine efficacy need to be considered in the context of testing and use of an AIDS vaccine. Public Library of Science 2010-03-23 /pmc/articles/PMC2843738/ /pubmed/20352116 http://dx.doi.org/10.1371/journal.pone.0009814 Text en Genescà et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Genescà, Meritxell
McChesney, Michael B.
Miller, Christopher J.
Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus
title Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus
title_full Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus
title_fullStr Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus
title_full_unstemmed Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus
title_short Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus
title_sort depo-provera® treatment does not abrogate protection from intravenous siv challenge in female macaques immunized with an attenuated aids virus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843738/
https://www.ncbi.nlm.nih.gov/pubmed/20352116
http://dx.doi.org/10.1371/journal.pone.0009814
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