A5040954811- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Tuberculosis Research and Epidemiology
- Adolescent Sexual and Reproductive Health
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- Pneumocystis jirovecii pneumonia detection and treatment
- vaccines and immunoinformatics approaches
- Reproductive tract infections research
- HIV-related health complications and treatments
- SARS-CoV-2 and COVID-19 Research
- Infectious Diseases and Tuberculosis
- Mycobacterium research and diagnosis
- Immunodeficiency and Autoimmune Disorders
- Hepatitis B Virus Studies
- Hepatitis C virus research
- HIV, Drug Use, Sexual Risk
- HIV/AIDS Impact and Responses
- COVID-19 Clinical Research Studies
- Antifungal resistance and susceptibility
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
Africa Health Research Institute
2016-2025
University of KwaZulu-Natal
2016-2025
Ragon Institute of MGH, MIT and Harvard
2016-2025
Massachusetts General Hospital
2009-2025
University College London
2018-2025
Institute of Infection and Immunity
2021-2025
Mass General Brigham
2025
Clinical Trial Investigators
2025
Max Planck Institute for Infection Biology
2015-2024
Massachusetts Institute of Technology
2011-2024
Abstract The emergence of the SARS-CoV-2 variant concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness lead to re-infections 1 . Here we investigated escape from neutralization by antibodies African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination who were previously infected or no evidence previous infection. isolated sequence-confirmed live virus an person observed that...
Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining health. However, little known about how microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women found that majority participants had communities with low abundance high ecological diversity. High-diversity strongly correlated pro-inflammatory cytokine concentrations both cross-sectional longitudinal analyses....
The human virome plays important roles in health and immunity. However, current methods for detecting viral infections antiviral responses have limited throughput coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antibodies using immunoprecipitation massively parallel DNA sequencing of bacteriophage library displaying proteome-wide peptides from all viruses. We assayed over 10(8) antibody-peptide interactions 569 humans across four continents, nearly...
HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected represent an extremely small proportion of all circulating possess remarkable long-term stability typically persist throughout life, for reasons are not fully understood. Here we performed massive single-genome,...
Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked pairs, the amino acid sequences encoded by non-envelope genes viruses both partners and demonstrate a selection bias residues that are predicted to confer increased vivo fitness on newly infected, immunologically naïve recipient. Although tempered risk factors, such as donor viral load, genital inflammation, recipient gender, this provides an overall...
Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization a strain evolved over 6 months ancestral virus person with advanced HIV disease South Africa; this was infected prior to emergence Beta and Delta variants. longitudinally tracked tested it against self-plasma convalescent plasma ancestral, Beta, infections. Early similar but multitude mutations found Omicron other It showed substantial...
Abstract The extent to which Omicron infection 1–9 , with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured neutralization capacity variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals South Africa infected sublineage BA.1 starting at a median 6 (interquartile range 3–9) days post symptom onset and continuing until last follow-up sample available, 23 19–27) symptoms allow...
HLA-B*57 is the class I allele most consistently associated with control of human immunodeficiency virus (HIV) replication, which may be linked to specific HIV peptides that this presents cytotoxic T lymphocytes (CTLs), and resulting efficacy these cellular immune responses. In two C clade-infected populations in South Africa Zambia, we sought elucidate role HLA-B*5703 disease outcome. HLA-B*5703-restricted CTL responses select for escape mutations three Gag p24 epitopes, a predictable...
Previous studies have identified a central role for HLA-B alleles in influencing control of HIV infection. An alternative possibility is that small number may very strong impact on disease outcome, dominating the contribution other HLA alleles. Here, we find even following exclusion subjects expressing any class I (B*57, B*58, and B*18) to strongest influence control, dominant virus set point absolute CD4 count variation remains significant. However, also this C-clade-infected cohort from...
Vinod Patel and colleagues evaluate the sensitivity specificity of quantitative PCR using Xpert MTB/RIF for diagnosis TB meningitis in high-burden setting South Africa. Please see later article Editors' Summary
Much uncertainty still exists over what T-cell responses need to be induced by an effective human immunodeficiency virus (HIV) vaccine. Previous studies have hypothesized that the CD8(+) are those driving selection of escape mutations reduce viral fitness and therefore revert post-transmission. In this study, we adopted a novel approach define better role reverting in immune control HIV infection. This analysis sequences from 710 study subjects with chronic C-clade type 1 infection...
Viral immune evasion by sequence variation is a major hindrance to HIV-1 vaccine design. To address this challenge, our group has developed computational model, rooted in physics, that aims predict the fitness landscape of proteins order design immunogens lead impaired viral fitness, thus blocking viable escape routes. Here, we advance models previous limitations, and directly test model predictions against vitro measurements strains containing multiple Gag mutations. We incorporated...
Human immunodeficiency virus type 1 (HIV-1) mutations that confer escape from cytotoxic T-lymphocyte (CTL) recognition can sometimes result in lower viral fitness. These then revert upon transmission to a new host the absence of CTL-mediated immune selection pressure restricted by HLA alleles prior host. To identify these potentially critical points on virus, we assessed HLA-driven evolution using three phylogenetic correction methods across full HIV-1 subtype C proteomes cohort 261 South...
Abstract Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell–cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool dissecting complex multicellular behaviors health disease 1,2 nominating testable therapeutic targets 3 . Its application to longitudinal samples could afford an opportunity uncover factors associated with the evolution of...
Inhibiting natural killer cells in AIDS The human leukocyte antigen (HLA) gene complex varies enormously among individuals and helps explain individual variation immunity to infectious diseases. Ramsuran et al. examined data from almost 10,000 HIV infections. Expression of the HLA-A - B alleles was associated with higher viral load, reduced CD4 + T cell counts, accelerated progression AIDS. Higher levels expression increased HLA-E , which blocks a specific receptor (NKG2A) on immune that...
ABSTRACT The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted with or identical binding motifs are known to target at different frequencies, functional avidities and apparent clinical outcomes. Such differences may be illuminated the association distinctive escape pathways. Using novel computational method featuring phylogenetically corrected odds...