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Antibody-based CCR5 blockade protects Macaques from mucosal SHIV transmission.
Nat Commun
June 2021
Vaccine & Gene Therapy Institute, Portland, OR, USA.
In the absence of a prophylactic vaccine, the use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition by uninfected individuals is a promising approach to slowing the epidemic, but its efficacy is hampered by incomplete patient adherence and ART-resistant variants. Here, we report that competitive inhibition of HIV Env-CCR5 binding via the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of CCR5-tropic SHIV. Injection of Leronlimab weekly at 10 mg/kg provides significant but partial protection, while biweekly 50 mg/kg provides complete protection from SHIV acquisition.
View Article and Find Full Text PDFInduction of HIV-blocking anti-CCR5 IgA in Peyers's patches without histopathological alterations.
J Virol
April 2014
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Unlabelled: The chemokine receptor CCR5 is essential for HIV infection and is thus a potential target for vaccine development. However, because CCR5 is a host protein, generation of anti-CCR5 antibodies requires the breaking of immune tolerance and thus carries the risk of autoimmune responses. In this study, performed in mice, we compared 3 different immunogens representing surface domains of murine CCR5, 4 different adjuvants, and 13 different immunization protocols, with the goal of eliciting HIV-blocking activity without inducing autoimmune dysfunction.
View Article and Find Full Text PDFNanoparticles containing siRNA to silence CD4 and CCR5 reduce expression of these receptors and inhibit HIV-1 infection in human female reproductive tract tissue explants.
Infect Dis Rep
September 2011
V.A. Medical Center, White River Junction, VT; ; Department of Microbiology & Immunology, Dartmouth Medical School, Lebanon, NH, USA.
Human Immunodeficiency Virus-type 1 (HIV-1) binds to CD4 and CCR5 receptors on target cells in the human female reproductive tract. We sought to determine whether reducing levels of messenger RNA (mRNA) transcripts that encode these receptors in female reproductive tract cells could protect mucosal tissue explants from HIV-1 infection. Explants prepared from the endometrium, endocervix, and ectocervix of hysterectomy tissues from HIV-1 sero-negative women were exposed to nanoparticles containing CD4- and CCR5-specific short-interfering RNA (siRNA) sequences.
View Article and Find Full Text PDFGeneration of a dual RT Env SHIV that is infectious in rhesus macaques.
J Med Primatol
August 2010
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD, TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Background: The best current animal model for HIV infection and evaluation of antiviral compounds is the Simian-human immunodeficiency virus (SHIV)/macaque system. There are multiple recombinant SHIVs available, but these viruses have limitations in evaluating combination drug strategies for prevention. Drug combinations that target reverse transcriptase (RT, either nRTI or nnRTI) and envelope (entry or fusion inhibitors) have to be tested separately, which does not permit the assessment of additive, synergistic, or antagonistic effects of ARV combinations.
View Article and Find Full Text PDFNatural mucosal antibodies reactive with first extracellular loop of CCR5 inhibit HIV-1 transport across human epithelial cells.
AIDS
January 2007
Institut Cochin, INSERM, CNRS, Paris, France.
Objective: The genital mucosa represents the major site for initial host-HIV-1 contact. HIV-1-protective mucosal immunity has been identified either in subjects who despite repeated sexual exposure, remain seronegative (ESN) or in long-term non-progressor HIV-1-seropositive individuals (LTNP). As a subset of ESN and LTNP produce anti-CCR5 antibodies both at systemic and mucosal level, we studied the role of anti-CCR5 antibodies in blocking HIV transfer through human epithelial cells.
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