A5072667047- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Parasites and Host Interactions
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Parasite Biology and Host Interactions
- Research on Leishmaniasis Studies
- Malaria Research and Control
- Trypanosoma species research and implications
- T-cell and B-cell Immunology
- Influenza Virus Research Studies
- Complement system in diseases
- Biochemical and Molecular Research
- Toxoplasma gondii Research Studies
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- Mycobacterium research and diagnosis
- Advanced Proteomics Techniques and Applications
- Trace Elements in Health
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- Tuberculosis Research and Epidemiology
PAI Life Sciences (United States)
2016-2025
University of Washington
2012-2024
Infectious Disease Research Institute
2012-2023
Alpine Immune Sciences (United States)
2020
Io Therapeutics (United States)
2020
Seattle University
2011-2020
Compliment Corporation (United States)
2012-2019
University of Washington Medical Center
2015-2019
New York Academy of Sciences
2018
John Wiley & Sons (United States)
2018
A nonhomologous integration vector was used to identify the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyl transferase (HXGPRT) gene by insertional mutagenesis. Parasite mutants resistant 6-thioxanthine arose at a frequency of ∼3 × 10−7. Genomic DNA flanking insertion sites retrieved marker rescue and molecular clones exhibiting unambiguous homology H(X)GPRT genes from other species. Sequence analysis vector/genome junction reveals that linearized occurred with minimal...
To assess the relationship between mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) clinical pyrimethamine-sulfadoxine resistance, polymerase chain reaction surveys analyses for new were conducted four countries with increasing levels of resistance: Mali, Kenya, Malawi, Bolivia. Prevalence at DHFR codon 108 a mutation DHPS 540 correlated increased resistance (P < .05). Mutations 51, 59, 437 without achieving statistical significance. 164...
Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 TRIF, leading the production inflammatory cytokines, type I interferons, chemokines. We report here characterization synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl adjuvant (GLA). assessed effects GLA murine human dendritic cells (DC) combining microarray, mRNA...
The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and global economy, highlighting urgent need for an effective vaccine. Such vaccine would to rapidly confer protection after one or two doses be manufactured using components suitable scale up. Here, we developed
Aluminum salts, developed almost a century ago, remain the most commonly used adjuvant for licensed human vaccines. Compared to more recently vaccine adjuvants, aluminum adjuvants such as Alhydrogel are heterogeneous in nature, consisting of 1-10 micrometer-sized aggregates nanoparticle oxyhydroxide fibers. To determine whether particle size and aggregated state affects its activity, we scalable, top-down process produce stable nanoparticles (nanoalum) from clinical by including poly(acrylic...
ABSTRACT Development of an effective vaccine against Leishmania infection is a priority tropical disease research. We have recently demonstrated protection major in the murine and nonhuman primate models with individual or combinations purified leishmanial recombinant antigens delivered as plasmid DNA constructs formulated interleukin-12 (IL-12) adjuvant. In present study, we immunized BALB/c mice polyprotein comprising tandem fusion thiol-specific antioxidant, L. stress-inducible protein 1...
The use of TLR agonists in vaccination broadens the range polymorphic variants against which antibodies can be effective.
Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular immune responses in both systemic mucosal compartments. Based on known immunological linkage between upper-respiratory urogenital tracts, we explored potential nasal adjuvants to boost immunization for vaginal gp140. Mice were immunized intranasally with gp140 together micellar emulsion formulations a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA) compared...
Recent reports that TLR4 and TLR7 ligands can synergistically trigger Th1 biased immune responses suggest an adjuvant contains both would be excellent candidate for co-administration with vaccine antigens which heavily are desired. Ligands of each these TLRs generally have disparate biochemical properties, however, straightforward co-formulation may represent obstacle. We show here the ligand, imiquimod, GLA, in human whole blood. combined anionic liposomal formulation where ligand is...
Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from hosts to humans. The severity infection in humans, as well sporadic nature outbreaks, both geographically and temporally, make generation an effective vaccine a global public health priority. An must ultimately provide protection against diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations demonstrated ability broaden responses pre-clinical models. However, many these...
Abstract Background There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection clinical trial enrollment by focusing on those most likely benefit from new interventions. Our objective was develop prognostic, model predicting mortality in adult Methods This secondary analysis using cohort of 252 mechanically ventilated subjects the diagnosis Survival day 7...
The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) is a potent Th1‐response‐inducing when formulated in squalene oil‐in‐water emulsion (SE). While the innate signals triggered by engagement are well studied, contribution of SE remains unclear. To better understand effect on properties GLA‐SE, we compared and adaptive immune responses elicited immunization with different formulations: GLA without oil, alone or combination, mice. Within response to adjuvants, only GLA‐SE displayed...
Reticulocyte invasion by
Current seasonal influenza virus vaccines engender antibody-mediated protection that is hemagglutinin (HA) subtype specific and relatively short-lived. Coverage for other subtypes or even variants within a could be improved from better understanding of the factors promote HA-specific antibody cross-reactivity. assays to evaluate cross-reactivity, such as ELISA, require separate test each antigen are neither high-throughput nor sample-sparing. To address this need, we produced an array 283...
An easy-to-use tuberculosis skin test is developed with chitin microneedles that deliver purified protein derivative at the correct depth and result in a positive BCG-immunized guinea pigs Microneedles combine transdermal delivery capabilities of hypodermic needles advantages dermal patches.1-4 Upon insertion, create small holes stratum corneum, outer most layer, to afford improved drug diffusion into dermis, similarly needles. At same time, application safe painless like patches.1...
We designed and produced a self-assembling protein nanoparticle. This nanoparticle contains five CD8
Abstract Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine urgently needed. Here, we report the results four independent, double‐blind studies Sm‐p80‐based baboons. The exhibited potent prophylactic efficacy against transmission Schistosoma mansoni infection and was associated with significantly less egg‐induced pathology, compared unvaccinated control animals. Specifically, resulted a 93.45% reduction pathology‐producing female...
Abstract A better understanding of the mechanisms action human adjuvants could inform a rational development next generation vaccines for use. Here, we exploited genome wide transcriptomics analysis combined with systems biology approach to determine molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules networks, which are shared or otherwise exclusive these clinical-grade...
Adjuvants are combined with vaccine antigens to enhance and modify immune responses, have historically been primarily crude, undefined entities. Introducing toll-like receptor (TLR) ligands has led a new generation of adjuvants, TLR4 being the most extensively used in human vaccines. The crystal structures demonstrate extensive contact their provide clues as how they discriminate broad array molecules activate or attenuate innate, well adaptive, responses resulting from these interactions....