Antiviral Antibodies and T Cells Are Present in the Foreskin of Simian Immunodeficiency Virus-Infected Rhesus Macaques

Rothaeusler, Kristina; Ma, Zhien; Qureshi, Huma; Carroll, Timothy D.; Rourke, Tracy; McChesney, Michael B.; Miller, Christopher J.

doi:10.1128/jvi.00410-12

Cited by 9 publications

(12 citation statements)

References 47 publications

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“…To date, there has been only one report of the presence of SIV-specific CD8 ϩ T cells in foreskin in SIV-infected rhesus monkeys (11). Consistent with this initial report, we also observed the presence of SIV-specific CD4 ϩ and CD8 ϩ T cells in the foreskin of SIV-and SHIV-infected animals.…”

Section: Discussionsupporting

confidence: 91%

“…Consistent with this initial report, we also observed the presence of SIV-specific CD4 ϩ and CD8 ϩ T cells in the foreskin of SIV-and SHIV-infected animals. Of note, SIV infection was performed via penile foreskin SIV exposure in the previous report (11), and thus our findings confirm and extend these previous data by showing SIV-specific CD4 ϩ and CD8 ϩ T cell responses in foreskin following intrarectal SIV and SHIV infection. Intriguingly, as observed previously (11), SIV-specific CD4 ϩ and CD8 ϩ T cells in foreskin appeared to secrete more TNF-␣ than SIVspecific T cells in peripheral blood.…”

Section: Discussionsupporting

confidence: 91%

“…SIV-specific CD8 ϩ T cells in foreskin have only been described in one prior study in SIV-infected rhesus monkeys infected by the penile route (11). To determine whether systemic SIV infection would similarly result in SIV-specific CD4 ϩ and CD8 ϩ T cells in foreskin, we assessed SIV Gag-specific CD4 ϩ and CD8 ϩ T cell responses in foreskin and peripheral blood of SIVand SHIV-infected animals infected by the intrarectal route.…”

Section: Systemic Immunization With Ad35/ad26-based Siv Vaccines and mentioning

confidence: 99%

“…However, little is known about HIV-1-specific immune responses in foreskin. To date, only one study has assessed simian immunodeficiency virus (SIV)-specific immune responses in foreskin of SIV-infected rhesus monkeys (11), and the potential induction and phenotype of SIV-or HIV-1-specific immune responses in foreskin following vaccination has not previously been explored. In the present study, we explore the hypothesis that vaccination may elicit potentially important cellular immune responses in foreskin.…”

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confidence: 99%

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Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Balandya

Miller

Beck

et al. 2014

J Virol

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Foreskin is the principal site of heterosexual HIV-1 infection in men. However, little is known about HIV-1-specific immune responses or inflammation in foreskin. To the best of our knowledge, no previous studies have assessed immune responses to candidate HIV-1 vaccines in foreskin. Using the rhesus monkey model, we show that intramuscular immunization with adenovirus serotype 26 and 35 vectors expressing SIV antigens elicited durable SIV Gag-specific CD4؉ and CD8 ؉ T cell responses in foreskin that were detectable for more than 1 year following vaccination. Gag-specific CD4؉ and CD8 ؉ T cells were also detectable in foreskin of SIV-and SHIV-infected animals and were at least comparable in magnitude to those in peripheral blood. However, unlike peripheral blood T cells, the majority of foreskin T cells exhibited transitional memory or effector memory phenotype and expressed higher levels of the activation markers CD69, HLA-DR, and CCR5, although vaccination did not further enhance foreskin CD4 ؉ T cell activation. These findings suggest that systemic vaccination strategies can elicit potentially important SIV-specific cellular immunity in foreskin. Further characterization of vaccine-elicited immune responses and inflammation in foreskin is warranted. IMPORTANCEWe demonstrate here the induction of SIV-specific cellular immune responses in foreskin by adenovirus serotype 26 and 35 vaccine vectors. Foreskin T cells were more activated than peripheral blood T cells, but foreskin T cells were not further activated by vaccination. These findings suggest that alternative serotype adenovirus vectors induce potentially important immune responses in foreskin.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Systemic Immunization With Ad35/ad26-based Siv Vaccines and mentioning

confidence: 99%

mentioning

confidence: 99%

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Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Balandya

Miller

Beck

et al. 2014

J Virol

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“…This area is at risk for HIV transmission. Again, the risk of transmission is greater if penile ulcers due to other STDs are present Ganor et al, 2010;Ma et al, 2011;Rothaeusler et al, 2012;Zhou et al, 2011). Mechanisms have been investigated for HIV-1 transmission across human foreskin organ cultures Ganor et al, 2010;Zhou et al, 2011) and for penile SIV transmission in rhesus macaques Rothaeusler et al, 2012) (see next section).…”

Section: Differences Between Vaginal Rectal and Oral Mucosal Transmmentioning

confidence: 97%

Human/Simian Immunodeficiency Virus Transmission and Infection at Mucosal Sites

Berzofsky

Franchini

2015

Mucosal Immunology

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Nonhuman Primate Models for HIV/AIDS Vaccine Development

et al. 2013

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The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

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Antiviral Antibodies and T Cells Are Present in the Foreskin of Simian Immunodeficiency Virus-Infected Rhesus Macaques

Abstract: No information exists regarding immune responses to human immunodeficiency virus (HIV) infection in

Cited by 9 publications

References 47 publications

Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Adenovirus Serotype 26 and 35 Vectors Induce Simian Immunodeficiency Virus-Specific T Lymphocyte Responses in Foreskin in Rhesus Monkeys

Human/Simian Immunodeficiency Virus Transmission and Infection at Mucosal Sites

Nonhuman Primate Models for HIV/AIDS Vaccine Development

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