A Phase 1, Single Center Study to Assess the Safety of MB66, a Combined Anti-HIV (VRC01-N) and Anti-HSV (HSV8-N) Monoclonal Antibody Film for Vaginal Application as Microbicide

The purpose of this study is to assess the safety and pharmacokinetics of MB66, a monoclonal antibody film for vaginal application that is being developed to potentially reduce the transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV).

Start Date01 Jan 2016

Sponsor / Collaborator

KBio Inc.

[+3]

NCT00122564

/ TerminatedPhase 1IIT

Phase I Study Evaluating the Systemic and Mucosal Safety and Immunogenicity of a Recombinant HIV-1 Gp 160 (MN/LAI) Administered by Transmucosal (Nasal or Vaginal) Routes, Alone or Formulated With DC-Chol, in HIV Negative Volunteers (ANRS VAC14)

It is probable that a mucosal approach is necessary for a prophylactic HIV vaccine protecting against sexually transmitted infection. Mucosal immune responses have been almost non-existent in trials of HIV vaccine candidates in which the antigen was delivered systemically. This study will test the safety and immune response of a recombinant HIV-1gp160 by nasal and mucosal routes alone or formulated with DC-Chol in healthy volunteers.

Start Date01 Jun 2003

Sponsor / Collaborator

National Agency for Research on AIDS and Viral Hepatitis

[+1]

NCT00004579

/ CompletedPhase 1IIT

A Phase I, Dose-Ranging Trial of the Pasteur Merieux Connaught (PMC) Oligomeric HIV-1 gp160MN/LAI-2 Vaccine Alone or Primed With Live Recombinant ALVAC-HIV (vCP205) in HIV Seronegative Adults

The purpose of this study is to see whether an HIV vaccine, ALVAC vCP205, is safe and can prevent HIV infection. The vCP205 vaccine will be tested with another vaccine, gp160MN/LAI-2.

Start Date01 Apr 1998

Sponsor / Collaborator

Walter Reed Army Institute of Research

100 Clinical Results associated with Envelope glycoprotein gp160

100 Translational Medicine associated with Envelope glycoprotein gp160

0 Patents (Medical) associated with Envelope glycoprotein gp160

Literatures (Medical) associated with Envelope glycoprotein gp160

01 Jan 2017·VirologyQ3 · MEDICINE

Sinu virus, a novel and divergent orthomyxovirus related to members of the genus Thogotovirus isolated from mosquitoes in Colombia

Q3 · MEDICINE

Article

Author: Juan David Suaza Vasco ; Robert B Tesh ; María Angélica Contreras-Gutiérrez ; Steven G Widen ; Sandra Uribe ; Vsevolod Leonidovich Popov ; Jedson Ferreira Cardoso ; Thomas G Wood ; Nikos Vasilakis ; Juan Carlos Gallego Gómez ; Hilda Guzman ; Marcio Roberto Teixeira Nunes

The genome and structural organization of a novel insect-specific orthomyxovirus, designated Sinu virus, is described. Sinu virus (SINUV) was isolated in cultures of C6/36 cells from a pool of mosquitoes collected in northwestern Colombia. The virus has six negative-sense ssRNA segments. Genetic analysis of each segment demonstrated the presence of six distinct ORFs encoding the following genes: PB2 (Segment 1), PB1, (Segment 2), PA protein (Segment 3), envelope GP gene (Segment 4), the NP (Segment 5), and M-like gene (Segment 6). Phylogenetically, SINUV appears to be most closed related to viruses in the genus Thogotovirus.

01 Nov 2015·Molecular and Cellular BiologyQ3 · BIOLOGY

Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder

Q3 · BIOLOGY

Article

Author: Kim, WooJin ; Power, Christopher ; Gelman, Benjamin ; Ramachandran, Rithwik ; Seidah, Nabil G. ; Essalmani, Rachid ; Hollenberg, Morley D. ; Susan-Resiga, Delia ; Marcinkiewicz, Edwidge ; Cohen, Éric A. ; Lodge, Robert ; Zekas, Erin ; Asahchop, Eugene ; Mihara, Koichiro

ABSTRACT The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg 41 ↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg 41 XXXXArg 46 ↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans -Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg 46 ↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND.

01 Mar 2014·Journal of VirologyQ2 · MEDICINE

Enhanced Central Nervous System Transduction with Lentiviral Vectors Pseudotyped with RVG/HIV-1gp41 Chimeric Envelope Glycoproteins

Q2 · MEDICINE

Article

Author: Mazarakis, Nicholas D. ; Liao, Ting-Yi ; Patsali, Petros ; Eleftheriadou, Ioanna ; Sgourou, Argyro ; Lee, Heyne ; Trabalza, Antonio

ABSTRACT To investigate the potential benefits which may arise from pseudotyping the HIV-1 lentiviral vector with its homologous gp41 envelope glycoprotein (GP) cytoplasmic tail (CT), we created chimeric RVG/HIV-1gp41 GPs composed of the extracellular and transmembrane sequences of RVG and either the full-length gp41 CT or C terminus gp41 truncations sequentially removing existing conserved motifs. Lentiviruses (LVs) pseudotyped with the chimeric GPs were evaluated in terms of particle release (physical titer), biological titers, infectivity, and in vivo central nervous system (CNS) transduction. We report here that LVs carrying shorter CTs expressed higher levels of envelope GP and showed a higher average infectivity than those bearing full-length GPs. Interestingly, complete removal of GP CT led to vectors with the highest transduction efficiency. Removal of all C-terminal gp41 CT conserved motifs, leaving just 17 amino acids (aa), appeared to preserve infectivity and resulted in a significantly increased physical titer. Furthermore, incorporation of these 17 aa in the RVG CT notably enhanced the physical titer. In vivo stereotaxic delivery of LV vectors exhibiting the best in vitro titers into rodent striatum facilitated efficient transduction of the CNS at the site of injection. A particular observation was the improved retrograde transduction of neurons in connected distal sites that resulted from the chimeric envelope R5 which included the “Kennedy” sequence (Ken) and lentivirus lytic peptide 2 (LLP2) conserved motifs in the CT, and although it did not exhibit a comparable high titer upon pseudotyping, it led to a significant increase in distal retrograde transduction of neurons. IMPORTANCE In this study, we have produced novel chimeric envelopes bearing the extracellular domain of rabies fused to the cytoplasmic tail (CT) of gp41 and pseudotyped lentiviral vectors with them. Here we report novel effects on the transduction efficiency and physical titer of these vectors, depending on CT length and context. We also managed to achieve increased neuronal transduction in vivo in the rodent CNS, thus demonstrating that the efficiency of these vectors can be enhanced following merely CT manipulation. We believe that this paper is a novel contribution to the field and opens the way for further attempts to surface engineer lentiviral vectors and make them more amenable for applications in human disease.

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