Abrogation of Attenuated Lentivirus‐Induced Protection in Rhesus Macaques by Administration of Depo‐Provera before Intravaginal Challenge with Simian Immunodeficiency Virus mac239

Abel, Kristina; Rourke, Tracy; Ding, Liang; Bost, Kristen; McChesney, Michael B.; Miller, Christopher J.

doi:10.1086/424600

Cited by 53 publications

(65 citation statements)

References 55 publications

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“…In nonhuman primates, DMPA treatment abrogates the generation of protective immunity to experimental HIV vaccines (7) and cellular responses to simian/human immunodeficiency virus (SHIV) infection (25). Therefore, we examined the effects of DMPA treatment on virus-induced APC activation.…”

Section: Dmpa Treatment Impairs Serum Ifn-␣ Responses To Viral Infectionmentioning

confidence: 99%

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Cutting Edge: Progesterone Regulates IFN-α Production by Plasmacytoid Dendritic Cells

Hughes

Thomas²,

Li³

et al. 2008

The Journal of Immunology

109

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Use of the progesterone (Pg) birth control depot medroxyprogesterone acetate (DMPA) increases a woman’s risk for sexually transmitted infection with HIV or HSV-2 via unknown mechanisms. Plasmacytoid dendritic cells (pDCs) are circulating and tissue-resident sentinels capable of making large quantities of IFN-α upon recognizing viruses through TLRs 7 and 9. In this study, we show that Pg inhibits TLR9-induced IFN-α production by human and mouse pDCs and that DMPA impairs TLR9- and virus-induced IFN-α production by pDCs in mice, providing a potential explanation for how DMPA impairs innate antiviral immunity in women. Pg failed to inhibit the Mda-5 pathway of IFN-α induction in dendritic cells, suggesting that Pg regulates select antiviral DC programs. This may occur through selective blockade of IFN regulatory factor-7 activation, a novel steroid action. Thus, through inhibition of TLR-mediated IFN-α production by pDCs, Pg may regulate antiviral immunity.

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Section: Dmpa Treatment Impairs Serum Ifn-␣ Responses To Viral Infectionmentioning

confidence: 99%

“…In nonhuman primates DMPA increases vaginal transmission of SIV (5), and in mice DMPA causes a 100-fold increased susceptibility to vaginal HSV-2 infection (6). DMPA also blocks development of protective antiviral immunity in these models (7). How Pg impairs innate and adaptive antiviral responses is poorly understood (8).…”

mentioning

confidence: 99%

Cutting Edge: Progesterone Regulates IFN-α Production by Plasmacytoid Dendritic Cells

Hughes

Thomas²,

Li³

et al. 2008

The Journal of Immunology

109

View full text Add to dashboard Cite

show abstract

“…A recent study showed that following treatment with medroxyprogesterone acetate, a progesterone formulation, protection from simian immunodeficiency virus was abolished in immunized monkeys (1). The authors concluded that treatment with progesterone decreased the efficacy of a model vaccine.…”

Section: Vol 79 2005 Hormone Effect On Hsv-2 Infection After Immunimentioning

confidence: 99%

“…Sim-ilar results have been seen in monkeys. In a recent study, treatment of rhesus macaques with medroxyprogesterone acetate prior to intravaginal (IVAG) challenge with simian immunodeficiency virus mac239 abolished attenuated vaccine-induced protection (1).…”

mentioning

confidence: 99%

Protection against Genital Herpes Infection in Mice Immunized under Different Hormonal Conditions Correlates with Induction of Vagina-Associated Lymphoid Tissue

Gillgrass

Tang

Towarnicki

et al. 2005

J Virol

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The present study was undertaken to examine the effect of the hormonal environment on immunization with an attenuated strain of herpes simplex virus type 2 (HSV-2 TK ؊ ) and subsequent protection against challenge. Ovariectomized mice were administered saline (S; control), estradiol (E 2 ), progesterone (P 4 ), or a combination of estradiol and progesterone (E؉P) and immunized intravaginally (IVAG) with HSV-2 TK ؊ . Three weeks later, the immunized mice were challenged IVAG with wild-type HSV-2. Mice that were immunized following E treatment were not protected, whereas complete protection against the challenge was seen in mice from the S-and P 4 -treated groups. In the P 4 -treated group, 15% of mice developed chronic pathology following TK ؊ immunization. Interestingly, about 40% of the E؉P-treated mice were also protected. Upon examination of viral shedding in the vaginal secretions, it was clear that protection against challenge was dependent on the ability of the TK ؊ virus to cause productive genital infection under different hormonal conditions. In the protected mice (the S and P groups and part of the E؉P group), induced vagina-associated lymphoid tissues composed of CD11c ؉ dendritic cells and CD3 ؉ and CD4 ؉ T cells were formed transiently in the vaginal lamina propria from day 2 to day 5 postchallenge. These aggregates were absent in the unprotected mice (the E group and part of the E؉P group). Significant HSV-2-specific activation of lymphocytes was observed in the local draining lymph nodes of protected mice. This response was absent in the unprotected groups. High titers of gB-specific local immunoglobulin A (IgA) antibodies were present in the vaginal secretions of S-and P 4 -treated immunized mice following HSV-2 challenge. The S-treated group of mice also had high gB-specific IgG titers. These studies show that sex hormones modify the induction of protective immune responses following IVAG immunization.In the past two decades, the incidence of sexually transmitted infections (STIs) has grown in virtually every country in the world (2), despite the fact that in this same time period there has been a continuous increase in resources and efforts devoted to controlling these infections. Although many of the STIs do not cause mortality, they are a major source of morbidity and financial burden on health systems globally. In addition, vertical transmission of these infections from mother to infant has serious sequelae. It is widely accepted that the best strategy to control these infections on a worldwide basis would be the development of efficacious prophylactic vaccines. Despite significant efforts, this goal, for the most part, remains elusive.Herpes simplex virus type 2 (HSV-2) infection is arguably the most common viral STI (18). A number of prophylactic and therapeutic vaccines have been designed and tested for the prevention and treatment of HSV-2 infections (16). In a recent subunit vaccine trial involving a truncated form of glycoprotein D of HSV-2, about 40% protection from disease was seen o...

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“…Progesterone, an estrogen antagonist, causes the epithelium to thin and therefore increases susceptibility. In addition to the thinning of the mucosa, progestins are reported to be immunosuppressive in macaque AIDS models and may contribute to disease progression or breaking vaccine protection [97,98]. Other factors in the vagina may also play a role, such as vaginal pH and thickening of mucous.…”

Section: Challenge Routes Of Infection For Testing Vaccine Efficacymentioning

confidence: 99%

Utility of Nonhuman Primate Models for Vaccines

Marx

Voevodin²

2012

Vaccinology

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Abrogation of Attenuated Lentivirus‐Induced Protection in Rhesus Macaques by Administration of Depo‐Provera before Intravaginal Challenge with Simian Immunodeficiency Virus mac239

Cited by 53 publications

References 55 publications

Cutting Edge: Progesterone Regulates IFN-α Production by Plasmacytoid Dendritic Cells

Cutting Edge: Progesterone Regulates IFN-α Production by Plasmacytoid Dendritic Cells

Protection against Genital Herpes Infection in Mice Immunized under Different Hormonal Conditions Correlates with Induction of Vagina-Associated Lymphoid Tissue

Utility of Nonhuman Primate Models for Vaccines

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