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OBJECTIVE Factors governing events between exposure of male genital mucosa surfaces and the establishment of infection are poorly understood. Furthermore, little is known about the safety and efficacy of microbicides on male genital mucosa. DESIGN Here we present a novel penile tissue explant model to characterize the mechanisms of HIV-1 infection of male(More)
The NGR peptide motif is an aminopeptidase N (CD13) ligand that targets angiogenic blood vessels. NGR-containing peptides have proven useful for delivering cytotoxic drugs, proapoptotic peptides, and tumor necrosis factor-alpha(TNF) to tumor vasculature. Given that CD13 is not only expressed in the angiogenic endothelium but also in other cell types, the(More)
Human immunodeficiency virus type 1 (HIV-1) subtype C is the dominant subtype globally, due largely to the incidence of subtype C infections in sub-Saharan Africa and east Asia. We compared the relative replicative fitness (ex vivo) of the major (M) group of HIV-1 subtypes A, B, C, D, and CRF01_AE and group O isolates. To estimate pathogenic fitness,(More)
A structurally novel candidate microbicide, PPCM, which is formed from the reaction of D,L-mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant(More)
In the present study we investigate the impact of a range of TLR ligands and chitosan as potential adjuvants for different routes of mucosal immunisation (sublingual (SL), intranasal (IN), intravaginal (IVag) and a parenteral route (subcutaneous (SC)) in the murine model. We assess their ability to enhance antibody responses to HIV-1 CN54gp140 (gp140) and(More)
Human immunodeficiency virus type 1 (HIV-1) transmission results from infection with one or a small number of variants from the donor quasispecies. Transmitted/founder (T/F) viruses have recently been identified from acutely infected patients, but the way in which they interact with primary targets of HIV-1 infection is poorly understood. We have conducted(More)
Delivering vaccine antigens to mucosal surfaces is potentially very attractive, especially as protection from mucosal infections may be mediated by local immune responses. However, to date mucosal immunization has had limited successes, with issues of both safety and poor immunogenicity. One approach to improve immunogenicity is to develop adjuvants that(More)
Methods Monocyte derived macrophages (MDMs) were isolated from PBMCs, while Monomac-1 cells were obtained from DSMZ. Expression of CD4, HIV-1 co-receptors and FcRs were analysed by FACS staining. Antibody inhibition was determined by p24 release. FcRs involvement was determined using blocking antibodies. Cytokine release was quantified by in house multiplex(More)
Methods Individual viruses (20) were evaluated for differential tropism in cellular assays (PBMC, monocyte-derived macrophages, PM1, TZM-bl cells, dendritic cells and dendritic cell-T cell trans-infection) and explant tissue assays, (ectocervix, penile glans, rectal and tonsil). Relative replication of each virus among the different models was assessed by(More)
Background The majority of HIV particles produced in vivo are noninfectious due to incorrectly processed or incomplete envelope spikes, and may act as potential decoys for humoral immunity. Specific targeting of the infectious subpopulations of virions by vaccine-induced antibodies may be required for sterilizing immunity. We have assessed the impact of(More)