A5108707946- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Immune responses and vaccinations
- HIV/AIDS Research and Interventions
- Advanced Biosensing Techniques and Applications
- Long-Term Effects of COVID-19
- Mosquito-borne diseases and control
- Malaria Research and Control
- Immunodeficiency and Autoimmune Disorders
- Tuberculosis Research and Epidemiology
- HIV/AIDS drug development and treatment
- Inflammasome and immune disorders
- Invertebrate Immune Response Mechanisms
- Vaccine Coverage and Hesitancy
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
Fred Hutch Cancer Center
2016-2025
RMIT Europe
2025
Agilent Technologies (United States)
2025
University of Washington
2014-2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2006-2023
Cancer Research Center
2008-2023
Infectious Disease Research Institute
2008-2023
Beth Israel Deaconess Medical Center
2021
Janssen (Belgium)
2021
Janssen (Netherlands)
2021
In the RV144 trial, estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed case–control analysis to identify antibody and cellular immune correlates infection risk.
Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding full-length and stabilized SARS-CoV-2 spike protein.In this multicenter, placebo-controlled, phase 1-2a trial, we randomly assigned healthy adults between ages 18 55 years (cohort 1) those 65 age...
Glutathione (GSH), a cysteine-containing tripeptide, is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression impair T cell suggested link between depletion disease progression. Clinical presented here directly demonstrate predict poor survival in otherwise indistinguishable HIV-infected subjects. Specifically, we show deficiency CD4 cells from such subjects associated with markedly decreased 2–3 years after...
Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 patients longitudinally up 8 months and find durable broad-based immune responses. SARS-CoV-2 spike binding neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting generation longer-lived plasma cells. infection also boosts antibody titers SARS-CoV-1 common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well...
<h3>Importance</h3> Developing effective vaccines against Ebola virus is a global priority. <h3>Objective</h3> To evaluate an adenovirus type 26 vector vaccine encoding glycoprotein (Ad26.ZEBOV) and modified vaccinia Ankara vaccine, glycoproteins from virus, Sudan Marburg Tai Forest nucleoprotein (MVA-BN-Filo). <h3>Design, Setting, Participants</h3> Single-center, randomized, placebo-controlled, observer-blind, phase 1 trial performed in Oxford, United Kingdom, enrolling healthy 18- to...
Flow cytometry is used increasingly in clinical research for cancer, immunology and vaccines. Technological advances instrumentation are increasing the size dimensionality of data sets, posing a challenge traditional management analysis. Automated analysis methods, despite general consensus their importance to future field, have been slow gain widespread adoption. Here we present OpenCyto, new BioConductor infrastructure framework designed lower barrier entry automated flow algorithms by...
Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute infection. The aetiologies may include persistent inflammation, unresolved tissue damage delayed clearance viral protein RNA, but the biological differences they represent are not fully understood. Here we evaluate serum proteome in samples, longitudinally collected from 55 PASC individuals with lasting ≥60 days after onset infection, comparison...
Background Glutathione (GSH) deficiency is common in HIV‐infected individuals and associated with impaired T cell function survival. N‐acetylcysteine (NAC) used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe effective replenishment HIV infection. Design Oral a randomized, 8‐week double‐blind, placebo‐controlled trial followed optional open‐label drug up 24 weeks. Subjects HIV‐infected, low GSH, CD4 cells < 500 μL −1...
Abstract Cytolytic enzymes (CEs) are critical mediators of anti-viral and -tumor immunity; however, as a number molecules belong to this enzyme family, our understanding CEs remains limited. Specifically, it unclear what combinations granzymes perforin (Perf) expressed by various immune cells how CE content relates cellular differentiation. Using polychromatic flow cytometry, we simultaneously measured expression the most common human [granzyme A (gA), granzyme B (gB), Perf] alongside...
Abstract In recent years, the quantification of T cell responses to pathogens or immunogens has become a common tool in evaluation disease pathogenesis vaccine immunogenicity. Such measurements are usually limited enumerating IFN-γ-producing cells after ex vivo stimulation with Ag, but little is known about phenotype complete functional repertoire Ag-specific cells. We used 12-color flow cytometry characterize elicited by vaccines natural infection determine lineage and differentiation...
To better understand how innate immune responses to vaccination can lead lasting protective immunity, we used a systems approach define signatures in humans over 1 wk following MRKAd5/HIV that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid trafficking occurred, lymphocyte-specific transcripts decreased. These alterations were corroborated by marked...
Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. One of their major limitations is that preexisting anti-vector neutralizing antibodies can reduce T cell responses the insert antigens; however, impact vector-specific cellular immunity on subsequent insert-specific has not been assessed in humans. Here, we have identified and compared adenovirus-specific HIV-specific subjects participating two HIV-1 vaccine trials...
Background The safety and immunogenicity of a vaccine regimen consisting 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by recombinant adenovirus serotype-5 (rAd5) with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America the Caribbean. Methods 480 were evenly randomized to receive either: (4 mg IM Biojector) at 0, 1 2 months, followed rAd5 (1010 PU needle/syringe) 6 months; or placebo. Participants monitored...
Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, ICOS, to identify potential CXCR5+CD4+ Tfh-like (cTfh) humans, investigated their functional phenotypes, diversity, ontogeny paired donor blood tonsils, after vaccination. Based receptor repertoire analysis,...
ABSTRACT BACKGROUND The ongoing coronavirus disease (COVID)-19 pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) might be controlled an efficacious vaccine. Multiple vaccines are in development, but no vaccine is currently available. METHODS We designed a multi-center phase 1/2a randomized, double-blinded, placebo-controlled clinical study to assesses the safety, reactogenicity and immunogenicity of Ad26.COV2.S, non-replicating adenovirus 26 based vector expressing...