Daniel J. Stieh
A5072872473- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Reproductive tract infections research
- Herpesvirus Infections and Treatments
- COVID-19 epidemiological studies
- Immunotherapy and Immune Responses
- Bacteriophages and microbial interactions
- Virology and Viral Diseases
- Reproductive System and Pregnancy
- Adolescent Sexual and Reproductive Health
- Hepatitis C virus research
- T-cell and B-cell Immunology
- Lipid Membrane Structure and Behavior
- Syphilis Diagnosis and Treatment
- Biosimilars and Bioanalytical Methods
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Transgenic Plants and Applications
Janssen (Netherlands)
2018-2025
Johnson & Johnson (Netherlands)
2024
Janssen (Switzerland)
2023
St George's, University of London
2009-2021
University of Pennsylvania
2017
John H. Stroger, Jr. Hospital of Cook County
2017
Northwestern University
2012-2016
University of London
2007-2008
St George's Hospital
2008
International Partnership for Microbicides
2007
Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared safety, tolerability, and immunogenicity a newly developed, tetravalent Ad26 vaccine with previously tested trivalent formulation.This randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a (TRAVERSE) was done at 11 centres in USA one centre Rwanda. Eligible participants were adults aged 18 to 50 years, who HIV-uninfected, healthy screening based on their...
HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis groups high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear stigma, concerns about side-effects, remain. Thus, population-based approach, an vaccine, is needed. The current study aimed...
The majority of new HIV infections occur in women as a result heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, avenues through which is established, and nature bottlenecks transmission, have been source considerable investigation contention. Using high dose single round non-replicating SIV-based vector containing novel dual reporter system, we determined sites by inoculum using rhesus macaque vaginal transmission model. Here show that...
Cells of the endocervix are responsible for secretion mucins, which provide an additional layer protection to female reproductive tract (FRT). This barrier is likely fortified with IgA as has previously been shown in gastrointestinal and lungs mice. Mucus associated can facilitate clearance bacteria. While a similar function IgG proposed, association mucus not yet demonstrated. Here we find that differentially different types FRT. We observed while both stably cervical mucus, only...
In the absence of a protective vaccine against human immunodeficiency virus (HIV), there is an urgent need for development effective topical microbicides to prevent HIV infection. Candidate vaginal should provide protection circulating strains, be cheap, stable on storage, safe and easy use. Here we describe detailed study safety efficacy Cyanovirin-N (CV-N) in vitro, ex vivo model female genital tissue explants. CV-N demonstrated potent activity low nanomolar range laboratory primary...
Abstract The quantitation of antibody responses is a critical requirement for the successful development vaccines and therapeutics that often relies on use standardized reference materials to determine relative quantities within biological samples. validity comparing across assays using arbitrarily defined values therefore limited. We developed generalizable method known as MASCALE ( Ma ss S pectrometry Enabled C onversion A bsolute L evels E LISA Antibodies) absolute antibodies by...
Objective: We sought to investigate the effects of HIV infection on vaginal microbiota and associations with treatment demographic factors. thus compared microbiome samples from HIV-infected (HIV+) HIV-uninfected (HIV−) women collected at two Chicago area hospitals. Design: studied 178 analyzed longitudinally (n = 324 samples) extensive data clinical status Methods: used 16S rRNA gene sequencing characterize bacterial lineages present, then UniFrac, Shannon diversity, other measures compare...
Abstract Background Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV. Methods This placebo-controlled, double-blind, phase 1/2a study enrolled healthy HIV-uninfected adults at low risk infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 encoding 2 mosaic Gag and Pol, Env proteins plus adjuvanted clade C gp140 (referred here as regimen), bivalent protein regimen (clade gp140), or placebo. Primary end points...
Abstract In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 and 1,067 placebo recipients who acquired this set of prespecified analyses, we show that in Latin America, VE significantly lower Lambda vs. Reference non-Lambda [family-wise error rate (FWER) p < 0.05]. differed by residue match mismatch...
Antibody capacity to recognize infectious virus is a prerequisite of many antiviral functions. We determined the virion capture index (IVCI) different antibody specificities. Whereas broadly neutralizing antibodies (bNAbs), except for an MPER bNAb, selectively captured virions, non-bNAbs and mucosal human immunodeficiency type 1 (HIV-1)-positive IgG subsets both noninfectious virions. Infectious was additive with mixture antibodies, providing proof concept vaccine-induced that together have improved
Abstract Several COVID-19 vaccines have recently gained authorization for emergency use. Limited knowledge on duration of immunity and efficacy these is currently available. Data other coronaviruses after natural infection suggest that to SARS-CoV-2 might be short-lived, preliminary evidence indicates waning antibody titers following infection. In this work, we model the relationship between immunogenicity protective a series Ad26 vectors encoding stabilized variants Spike protein in rhesus...
Although clade-specific and cross-clade mosaic prime–boost HIV-1 vaccine regimens were advanced to the HVTN 702 705 efficacy trials, neither regimen prevented HIV acquisition. The respective Phase 1/2a studies, 100 (NCT02404311) 117/HPX2004 (NCT02788045), provided rich immunological data, including previously identified correlates of risk, for comparing immune responses elicited by these over time. We analyzed antibody measured binding multiplex assay, CD4+ CD8+ T-cell intracellular cytokine...
Mannose-binding C-type lectin receptors, expressed on Langerhans cells and subepithelial dendritic (DCs) of cervico-vaginal tissues, play an important role in HIV-1 capture subsequent dissemination to lymph nodes. DC-SIGN has been implicated both productive infection DCs the DC-mediated trans CD4+ T that occurs absence replication. However, molecular events underlie this efficient transmission have not fully defined. In study, we examined effect extracellular domains Langerin stability...
Antibody mediated viral aggregation may impede transfer across mucosal surfaces by hindering movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible CD4 T cells and dendritic cells. These functions work together provide effective immune exclusion virus from tissue; however little is known about the antibody characteristics required induce HIV aggregation. Such knowledge be critical design successful immunization...
Human immunodeficiency virus type 1 (HIV-1) transmission results from infection with one or a small number of variants the donor quasispecies. Transmitted/founder (T/F) viruses have recently been identified acutely infected patients, but way in which they interact primary targets HIV-1 is poorly understood. We conducted biological characterization panel subtype B T/F acute and chronic envelope (Env)-expressing chimeric human target cells mucosal tissues. Both Envs preferentially replicated...
Abstract Anti-spike IgG binding antibody, anti-receptor domain and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk moderate to severe-critical COVID-19 outcomes through 83 days protection following a single dose Ad26.COV2.S vaccine in the placebo-controlled phase ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence correlate protection, with strongest for 50% inhibitory dilution (ID50) titer. The...
Abstract Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety immunogenicity of 2 mosaic vaccine regimens virologically suppressed individuals initiated ART chronic phase infection, exemplifying majority PLWH. In this double-blind, placebo-controlled 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized receive...
Abstract Assessment of immune correlates severe COVID-19 has been hampered by the low numbers cases in vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as risk protection against severe-critical through 220 days post-vaccination ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous analysis enabling inclusion 42 vaccine-breakthrough cases. Neutralizing titer is a strong inverse...
ABSTRACT Early stages of mucosal infection are potential targets for HIV-1 prevention. CD4 is the primary receptor in whereas DC-SIGN likely plays an important role dissemination, particularly during sexual transmission. To test hypothesis that inhibitor simultaneously targeting both and binding sites on gp120 may provide a potent anti-HIV strategy, we designed constructs by fusing extracellular domains together with varied arrangements lengths CD4, linker. We expressed, purified...