A5022835999- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Enzyme function and inhibition
- Monoclonal and Polyclonal Antibodies Research
- Renin-Angiotensin System Studies
- vaccines and immunoinformatics approaches
- Peptidase Inhibition and Analysis
- ATP Synthase and ATPases Research
- Mosquito-borne diseases and control
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Biochemical and Molecular Research
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Zoonotic diseases and public health
- Dengue and Mosquito Control Research
- Viral Infections and Outbreaks Research
- Genomics and Rare Diseases
- Lipid Membrane Structure and Behavior
University of Cape Town
2012-2023
National Health Laboratory Service
2016
Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. This forms even when ART initiated early after infection, but dynamics of its formation are largely unknown. The viral reservoirs individuals who initiate chronic infection generally larger and genetically more diverse than those acute consistent with hypothesis that formed continuously throughout untreated infection. To...
The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. viruses isolated from AMP participants who acquired infection during study in sub-Saharan African (HVTN 703/HPTN 081) Americas/European 704/HPTN 085) represent a panel of currently circulating strains offer unique opportunity to investigate...
ABSTRACT V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate development these can provide insights for immunogen design. We used deep-sequencing approach, together with neutralization phenotyping, to investigate rate and complexity escape from V3-glycan-directed bNAbs compared overlapping early strain-specific antibody (ssNAb) responses V3/C3 region in donor CAP177. Escape ssNAb response...
Human ACE (angiotensin-I-converting enzyme) has long been regarded as an excellent target for the treatment of hypertension and related cardiovascular diseases. Highly potent inhibitors have developed are extensively used in clinic. To develop with higher therapeutic efficacy reduced side effects, recent efforts directed towards discovery compounds able to simultaneously block more than one zinc metallopeptidase (apart from ACE) involved blood pressure regulation humans, such neprilysin...
ABSTRACT All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly antibodies. Defining the epitopes of that overlap conserved sites vulnerability might provide mechanistic insights how arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed plasma targeting N276 glycan-dependent epitope CD4 binding site. The initial site response potently neutralized heterologous tier 2 B...
Early 2019, a chikungunya virus (CHIKV) outbreak hit the Democratic Republic of Congo (DRC). Though seldomly deadly, this mosquito-borne disease presents as an acute febrile (poly)arthralgia often followed by long-term sequelae. Although Aedes aegypti is primary vector, amino acid substitution in viral envelope gene E1 (A226V) causing concern it results increased transmission albopictus, mosquito with much wider geographical distribution. Between January and March we collected human samples...
Neutralizing antibodies (nAbs) to highly variable viral pathogens show remarkable diversification during infection, resulting in an "arms race" between virus and host. Studies of nAb lineages have shown how somatic hypermutation (SHM) immunoglobulin (Ig)-variable regions enables maturing neutralize emerging escape variants. However, the Ig-constant region (which determines isotype) can also influence epitope recognition. Here, we use longitudinal deep sequencing HIV-directed lineage,...
Knowledge of the time HIV-1 infection and multiplicity viruses that establish is crucial for in-depth analysis clinical prevention efficacy trial outcomes. Better estimation methods would improve ability to characterize immunological genetic sequence correlates within preventive trials vaccines monoclonal antibodies. We developed new timing using maximum likelihood estimators shift scale (calibrate) estimates by fitting true times founder virus multiplicities a linear regression model with...
Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of enables the to rapidly adapt, and thus viral escape a very sensitive approach demonstrate importance this response. To enable us deconvolute ADCC neutralizing antibody (nAb) escape, we identified individuals soon after infection with detectable responses, but no nAb responses. We evaluated...
Within an individual living with HIV-1, factors that restrict the movement of HIV-1 between different compartments—such as blood and male genital tract—could strongly influence which viruses reach sites in body from they can be transmitted. Using deep sequencing, we found strong evidence restricted movements tract all 10 men studied. We additionally neither degree to particular genetic variants proliferate (in or tract) nor individual’s history sexually transmitted infections detectably...
Abstract Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. Little known about dynamics of formation and this forms even when ART initiated early after infection. The individuals who initiate chronic infection generally larger genetically more diverse than that acute infection, suggesting formed continuously throughout untreated To determine viruses enter reservoir, we...
HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective prevention requires combination of approaches understanding, analyzing, debating the cross-cutting issues impact research are all essential to combat global HIV/AIDS epidemic. To end, biennial HIVR4P conference is dedicated biomedical approaches, including vaccines, microbicides, pre-exposure prophylaxis, treatment as prevention. The 2016 held in...