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

Meritxell Genescá, Michael B. McChesney, Chris J Miller

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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-c 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- ProveraH 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.

Original languageEnglish (US)
Article numbere9814
JournalPLoS One
Volume5
Issue number3
DOIs
StatePublished - 2010

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
Medroxyprogesterone Acetate
Macaca
Viruses
Animals
HIV
viruses
Progesterone
progesterone
virus replication
animals
contraceptives
T-cells
Contraceptive Agents
Therapeutics
Haplorhini
monkeys
Contraceptive Vaccines
T-lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Depo-Provera® Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus. / Genescá, Meritxell; McChesney, Michael B.; Miller, Chris J.

In: PLoS One, Vol. 5, No. 3, e9814, 2010.

Research output: Contribution to journalArticle

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title = "Depo-Provera{\circledR} Treatment Does Not Abrogate Protection from Intravenous SIV Challenge in Female Macaques Immunized with an Attenuated AIDS Virus",
abstract = "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{\circledR} 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{\circledR}, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to na{\"i}ve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera{\circledR} 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-c 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{\circledR} 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- ProveraH 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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