A5058482085- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Vaccine Coverage and Hesitancy
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- HIV, Drug Use, Sexual Risk
- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Long-Term Effects of COVID-19
- HIV/AIDS Research and Interventions
- Immune responses and vaccinations
- COVID-19 epidemiological studies
- Viral Infections and Outbreaks Research
- Diagnosis and treatment of tuberculosis
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
Africa Health Research Institute
2018-2023
University College London
2020-2023
Centre for the AIDS Programme of Research in South Africa
2022
Institute of Infection and Immunity
2021
Max Planck Institute for Infection Biology
2021
University of KwaZulu-Natal
2018-2020
Assessment of the safety and efficacy vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as investigation emerging SARS-CoV-2 variants concern, including B.1.351 (501Y.V2) variant first identified South Africa.
Abstract Background Assessing safety and efficacy of Covid-19 vaccines in different populations is essential, as investigation against emerging SARS-CoV-2 variants concern including the B.1.351 (501Y.V2) variant first identified South Africa. Methods We conducted a randomized multicentre, double blinded controlled trial on ChAdOx1-nCoV19 HIV-uninfected people Participants age 18 to <65 years (1:1) two doses vaccine containing 5×10 10 viral particles or placebo (0.9%NaCl) 21-35 days apart....
There are conflicting reports on the effects of HIV COVID-19. Here, we analyzed disease severity and immune cell changes during after SARS-CoV-2 infection in 236 participants from South Africa, which 39% were people living with (PLWH), first second (Beta dominated) waves. The wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher was associated low CD4 T counts higher neutrophil lymphocyte ratios (NLR). Yet, recovered NLR stabilized clearance 2...
Abstract There are conflicting reports on the effects of HIV COVID-19. Here we analyzed disease severity and immune cell changes during after SARS-CoV-2 infection in 236 participants from South Africa, which 39% were people living with (PLWH), first second ( β dominated) waves. The wave had more PLWH requiring supplemental oxygen relative to negative participants. Higher was associated low CD4 T counts higher neutrophil lymphocyte ratios (NLR). Yet, recovered NLR stabilized clearance 2...
Abstract Viruses increase the efficiency of close-range transmission between cells by manipulating cellular physiology and behavior, SARS-CoV-2 uses cell fusion as one mechanism for cell-to-cell spread. Here we visualized infection using time-lapse microscopy a human lung line used live virus neutralization to determine sensitivity spread neutralizing antibodies. rapidly led fusion, forming multinucleated with clustered nuclei which started be detected at 6h post-infection. To compare...
Introduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates cellular interaction between Mtb macrophages. We aimed to characterize growth within Methods: utilized live cell tracking through time-lapse microscopy better understand biological effect in response infection. Furthermore, potent...
Abstract One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved such infection, we tested SARS-CoV-2 viruses from an ancestral B.1 lineage lasting over 190 days post-diagnosis advanced HIV disease individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with second sub-lineage replacing first a seeming evolutionary sweep. Each independently escape neutralizing antibodies....
Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined transcriptional response of human monocyte derived macrophages phagocytosis aggregated relative non-aggregated single or multiple bacilli. Infection with led an early upregulation pro-inflammatory associated genes enhanced TNFα signaling via NFκB pathway. These pathways were...
Abstract The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS-CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction cell fusion and death evolved from ancestral virus during long-term infection. Both were BA.1 virus. Evolved was isolated at different times a 6-month an immunosuppressed individual with advanced HIV disease. 16 days post-reported symptom onset induced fusogenicity...
HIV infection can be cleared with antiretroviral drugs if they are administered before exposure, where exposure occurs at low viral doses which infect one or few cells. However, clearance does not happen once is established, and this may because of the very early formation a reservoir latently infected Here we investigated whether initial dose could sub-optimal drug inhibition allows ongoing replication, hence require latency for persistence. We derived model inputs being effects on...
Abstract In this South African phase 1/2b study, we demonstrated vaccine efficacy (VE) of two doses AZD1222 for asymptomatic and symptomatic SARS-CoV-2 infection: 90.6% against wild-type 77.1% the Delta variant ≥9 months after vaccination. VE infection with Beta variant, which preceded circulation Delta, was 6.7%. Clinical trial identifier CT.gov NCT04444674
Abstract Pre-exposure prophylaxis (PrEP) uses relatively weak HIV inhibition to reduce transmission between individuals. Why this approach is successful unclear. Here we derive and experimentally validate a mathematical model for predicting infection clearance with PrEP based on the measured effect of drug replication ratio number initial infected cells. We tested by inhibiting low dose tenofovir, which reduces frequency per cell, atazanavir, cellular burst size viable virions. Both drugs...
Abstract Mycobacterium tuberculosis (Mtb) readily aggregates in culture and Mtb the lung were observed experimental infection. However, physiological consequences of aggregation are incompletely understood. Here we examined human macrophage transcriptional response to aggregated relative infection with non-aggregated single or multiple bacilli per host cell. Infection led an early upregulation pro-inflammatory associated genes enhanced TNF α signaling via NF κ B pathway. Both these pathways...