A5089579849- HIV Research and Treatment
- Herpesvirus Infections and Treatments
- Reproductive tract infections research
- HIV/AIDS Research and Interventions
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Adolescent Sexual and Reproductive Health
- Virus-based gene therapy research
- Immune Response and Inflammation
- Virology and Viral Diseases
- T-cell and B-cell Immunology
- Antimicrobial Peptides and Activities
- Cervical Cancer and HPV Research
- interferon and immune responses
- Sex work and related issues
- Seaweed-derived Bioactive Compounds
- Hepatitis Viruses Studies and Epidemiology
- Freezing and Crystallization Processes
- Systemic Lupus Erythematosus Research
- Probiotics and Fermented Foods
- Dermatology and Skin Diseases
- vaccines and immunoinformatics approaches
- Echinoderm biology and ecology
Population Council
2010-2019
SimulConsult
2018
Population Council
2007-2015
Foundation for Biomedical Research
2007-2008
Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out explore the antiviral properties GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) human papillomavirus (HPV) as well determine mechanism action (MOA) both viruses. performed experiments in different cell lines, using time-of-addition temperature dependence differentiate inhibition viral attachment from entry receptor...
Background Repeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb spread. Current formulations require high doses (millimolar range) of drugs and typically only provide short-term protection in macaques. We the macaque model test efficacy a novel combination gel containing zinc acetate micromolar non-nucleoside reverse transcriptase inhibitor MIV-150 for up 24 h after repeated application....
Abstract Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options individuals who become infected. Moreover, on-demand products are currently missing from PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived red algae an excellent safety profile potent activity vitro. When combined...
Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, although several reports describe interaction between these two viruses, exact mechanism for this increased susceptibility remains unclear. Dendritic cells (DCs) at site entry HSV-2 and contribute to viral spread in mucosa. Specialized DCs present gut-associated lymphoid tissues produce retinoic acid (RA), an important immunomodulator, able influence replication a key mediator integrin α4β7 on lymphocytes. can be...
In Brief Objective: The objective of this article is to study the effect PC-815, a novel combination microbicide containing carrageenan and nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150, in blocking HIV-1 HIV-2 infections vitro as compared with Carraguard alone. Goal: goal was develop that more efficacious than against HIV-2. Study Design: microtiter syncytial assay used evaluate: 1) antiviral virucidal activity MIV-150 HIV-1MN; 2) additive when combined carrageenan; 3)...
Anti-HIV microbicides are being investigated in clinical trials and understanding how promising strategies work, coincident with demonstrating efficacy vivo, is central to advancing new generation microbicides. We evaluated Carraguard a Carraguard-based formulation containing the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 (PC-817). Since dendritic cells (DCs) believed be important HIV transmission, formulations were tested for ability limit DC-driven infection vitro...
ABSTRACT Human immunodeficiency virus (HIV) is taken up by and replicates in immature dendritic cells (imDCs), which can then transfer to T cells, amplifying the infection. Strategies known boost DC function were tested for their ability overcome this exploitation when added after HIV exposure. Poly(I:C), but not single-stranded RNA (ssRNA) or a standard maturation cocktail, elicited type I interferon (IFN) interleukin-12 (IL-12) p70 production appearance of unique small (15- 20-kDa)...
ABSTRACT Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce incidence infections worldwide. Previously we completed phase 3 testing carrageenan-based gel Carraguard. Although trial did not show Carraguard is effective in preventing during vaginal sex, it safe when used weekly for up years. Moreover, has vitro activity against human papillomavirus (HPV) HSV-2 favorable physical rheological properties, which makes...
Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity osmolality of popular lubricants. A total 41 were examined compared to Gynol II Carraguard as positive negative controls toxicity, respectively. Cytotoxicity was assessed using XTT assay. The MAGI assay with R5 X4 HIV-1 laboratory strains...
Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased HIV-1 acquisition) prevents unintended pregnancy. Here, we describe novel core–matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered MZC combination microbicide contraceptive. The IVR contains four active pharmaceutical ingredients (APIs): MIV-150 (targets HIV-1), zinc acetate (ZA;...
Commercial vaccines against human papillomavirus (HPV) have low uptake due to parental autonomy, dosing regimen, cost, and cold chain storage requirements. Carrageenan (CG)-based formulations prevent HPV infection in vitro vivo but data are needed on the durability of anti-HPV activity effect seminal plasma (SP). The Population Council's PC-515 gel lubricant Divine 9 were tested for their physicochemical properties HPV16, 18, 45 pseudoviruses (PsVs). Anti-PsV was estimated using luciferase...
An intravaginal ring loaded with the NNRTI MIV-150 prevents transmission of HIV/SIV chimera SHIV-RT in macaques.
Integrin α₄β₇(high) (α₄β₇(high)) mediates the homing of CD4⁺ T cells to gut-associated lymphoid tissues, which constitute a highly favorable environment for HIV expansion and dissemination. simian immunodeficiency virus (SIV) envelope proteins bind signal through during acute infection SIV preferentially infects cells. We postulated that availability these at time challenge could influence mucosal transmission viral load (VL).We challenged 17 rhesus macaques with 3000 TCID50 SIVmac239...
Prevalent infection with human herpes simplex 2 (HSV-2) or papillomavirus (HPV) is associated increased immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well these sexually transmitted infections (STIs) may more effectively limit incidence. Previously, we showed a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human (SHIV-RT) ZC mice HSV-2 infection. Here evaluated modified MZC (containing different...
Here, we describe the generation of a novel type HIV entry inhibitor using recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from DNA library ribosome display. Selected pool members interacted specifically with and competed gp120 binding to CD4. derived in initial selection series inhibited dose-dependent manner, but showed relatively high variability their capacity block replication patient isolates on primary T...
Background Herpes simplex virus type-2 (HSV-2) infection enhances the transmission and acquisition of human immunodeficiency (HIV). This occurs in symptomatic asymptomatic stages HSV-2 infection, suggesting that obvious herpetic lesions are not required to increase HIV spread. An animal model investigate underlying causes synergistic action two viruses where preventative strategies can be tested under such complex physiological conditions is currently unavailable. Methodology/Principal...
Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and zinc (ZA/CG) significantly protected macaques from simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day 4 weeks, the animals challenged 4-24 h later. Herein, examined effects single dose administered before after challenge. Encouraged by protection seen with MIV-150/ZA/CG, also tested it...
ABSTRACT Development of a microbicide that prevents rectal transmission human immunodeficiency virus (HIV) is vital component in reducing HIV spread. We recently demonstrated formulation the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 carrageenan reduced vaginal infection macaques with simian SIVmac239 HIV-1 HxB2 (SHIV-RT). Herein, we performed first testing MIV-150–carrageenan against infection. Rhesus were treated rectally or methyl cellulose (MC) placebo gel up to 4 h...
The availability of highly susceptible HIV target cells that can rapidly reach the mucosal lymphoid tissues may increase chances an otherwise rare transmission event to occur. Expression α4β7 is required for trafficking immune gut inductive sites where expand and it expressed at high level on particularly infection. We hypothesized HSV-2 modulates expression other homing receptors in vaginal tissue this correlates with increased risk acquisition positive individuals. To test hypothesis we...
Several studies suggest that progesterone and estrogens may affect HIV transmission in different, possibly opposing ways. Nonetheless, a direct comparison of their effects on the mucosal immune system has never been done. We hypothesize sex hormones might impact availability cells factors important early stages transmission, and, doing so influence risk acquisition. To test this hypothesis, we employed 15 ovarectomized rhesus macaques: 5 were treated with Depot Medroxy Progesterone Acetate...
ABSTRACT We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well macaques simian-human immunodeficiency reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers cosolvents to obtain stable, nearly iso-osmolal formulation evaluated its safety efficacy SHIV-RT HSV-2. vitro toxicity lactobacilli Candida albicans was determined. Macaques were given...
ABSTRACT Here, we applied the designed ankyrin repeat protein (DARPin) technology to develop novel gp120-directed binding molecules with HIV entry-inhibiting capacity. DARPins are interesting for envelope inhibitor design, as their high-affinity differs from that of antibodies. in general prefer epitopes a defined folded structure. We probed whether this capacity favors selection gp120-reactive specificities epitope recognition and inhibitory activity differ those found among neutralizing...
Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers exhausted CD21neg memory cells, driven continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this phenotype also prevalent among peripheral antigen-inexperienced naive marginal zone (MZ) acute chronic A substantial fraction MZ exhibit down-regulated CD21 levels diminished response to cell receptor (BCR)–dependent stimulation. Compared...