The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

Wang, Yichuan; Abel, Kristina; Lantz, Katherine; Krieg, Arthur Μ.; McChesney, Michael B.; Miller, Christopher J.

doi:10.1128/jvi.79.22.14355-14370.2005

Cited by 119 publications

(83 citation statements)

References 81 publications

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“…It has been previously observed that the induction of innate immune responses at the vaginal mucosa through TLR ligands prior to SIV inoculation does not protect macaques from infection and elicited a broad range of immune modulators (64). In contrast, Li et al recently demonstrated that the specific inhibition of certain proinflammatory cytokines and chemokines such as macrophage inflammatory protein 3␣ (MIP-3␣) at the vaginal mucosa prior to challenge could prevent vaginal transmission of SIV, possibly by preventing the recruitment of CCR5-bearing cells to the site of virus exposure (33).…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys

Durudas

Milush

Chen

et al. 2009

J Virol

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؉ cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV ؉ monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-␣, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV ؉ patients, which could lead to novel therapy and vaccine approaches.

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Section: Discussionmentioning

confidence: 99%

Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys

Durudas

Milush

Chen

et al. 2009

J Virol

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“…A number of studies have been carried out in macaques (27)(28)(29) and women (24,30), in which the vaginal mucosal route of immunization of HIV-1 antigens was compared with the systemic, oral, or nasal route of immunization. The subjects were free of adverse effects, and the immunizations yielded variable immune responses, depending on the immunogen, adjuvant, the combined route of immunization, and the parameters investigated.…”

Section: Discussionmentioning

confidence: 99%

Effect of Vaginal Immunization with HIVgp140 and HSP70 on HIV-1 Replication and Innate and T Cell Adaptive Immunity in Women

Lewis

Wang

Huo

et al. 2014

J Virol

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The international effort to prevent HIV-1 infection by vaccination has failed to develop an effective vaccine. The aim of this vaccine trial in women was to administer by the vaginal mucosal route a vaccine consisting of HIV-1 gp140 linked to the chaperone 70-kDa heat shock protein (HSP70). The primary objective was to determine the safety of the vaccine. The secondary objective was to examine HIV-1 infectivity ex vivo and innate and adaptive immunity to HIV-1. Protocol-defined female volunteers were recruited. HIV-1 CN54gp140 linked to HSP70 was administered by the vaginal route. Significant adverse reactions were not detected. HIV-1 was significantly inhibited ex vivo in postimmunization CD4؉ T cells compared with preimmunization CD4 ؉ T cells. The innate antiviral restrictive factor APOBEC3G was significantly upregulated, as were CC chemokines which induce downregulation of CCR5 in CD4 ؉ T cells. Indeed, a significant inverse correlation between the proportion of CCR5 ؉ T cells and the concentration of CCL-3 or CCL-5 was found. Importantly, the upregulation of APOBEC3G showed a significant inverse correlation, whereas CCR5 exhibited a trend to correlate with inhibition of HIV-1 infection (r ‫؍‬ 0.51). Furthermore, specific CD4 ؉ and CD8 ؉ T cells showed HIVgp140-and HSP70-specific proliferation. A strong inverse correlation between the proportion of CC chemokine-modulated CCR5-expressing CD4 ؉ T cells and the stimulation of CD4 ؉ or CD8 ؉ T cell proliferation by HIVgp140 was found, demonstrating a significant interaction between innate and adaptive immunity. This is the first clinical trial of vaginal immunization in women using only HIVgp140 and HSP70 administered by the mucosal route (3 times) in which a dual innate protective mechanism was induced and enhanced by significant adaptive CD4 ؉ and CD8 ؉ T cell proliferative responses.

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“…These signals in combination with innate immune signals and inflammatory cells lead to recruitment of CD4+ T cells for HIV dissemination. Additionally, TLR7 and TLR9 agonists do not prevent vaginal transmission of SIV when intravaginally applied to rhesus macaques [61]. These agonists induce mucosal IFN production and recruitment of immune cells but increase plasma viral load.…”

Section: In Vitro Effect Of Gc Infection Of Hiv Target Cellsmentioning

confidence: 99%

Modulation of HIV Transmission by Neisseria gonorrhoeae: Molecular and Immunological Aspects

Jarvis¹,

Chang²

2012

CHR

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Neisseria gonorrhoeae (GC), a major cause of pelvic inflammatory disease, can facilitate HIV transmission. In response to GC infection, genital epithelial cells can produce cytokines, chemokines and defensins to modulate HIV infection and infectivity. GC can also induce the production of cytokines and chemokines in monocytes and modulate T cell activation. In vivo, an increase in the number of endocervical CD4+ T cells has been found in GC-infected women. Additionally, GC appears to modulate HIV-specific immune responses in HIV-exposed sex workers. Interestingly, in vitro, GC exhibits HIV enhancing or inhibitory effects depending on the HIV target cells. This review summarizes molecular and immunological aspects of the modulation of HIV infection and transmission by GC. Future studies using a multi-cellular system or in animal models will offer insight into the mechanisms by which GC increases HIV transmission.

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The Toll-Like Receptor 7 (TLR7) Agonist, Imiquimod, and the TLR9 Agonist, CpG ODN, Induce Antiviral Cytokines and Chemokines but Do Not Prevent Vaginal Transmission of Simian Immunodeficiency Virus When Applied Intravaginally to Rhesus Macaques

Cited by 119 publications

References 81 publications

Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys

Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys

Effect of Vaginal Immunization with HIVgp140 and HSP70 on HIV-1 Replication and Innate and T Cell Adaptive Immunity in Women

Modulation of HIV Transmission by Neisseria gonorrhoeae: Molecular and Immunological Aspects

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