A5101885731- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Reproductive System and Pregnancy
- Pneumonia and Respiratory Infections
- Inflammasome and immune disorders
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Curcumin's Biomedical Applications
- Inhalation and Respiratory Drug Delivery
- Pancreatitis Pathology and Treatment
- Drug Transport and Resistance Mechanisms
- Protein purification and stability
- Escherichia coli research studies
- Influenza Virus Research Studies
- Parasitic Infections and Diagnostics
- Malaria Research and Control
- Parasites and Host Interactions
- Pediatric Hepatobiliary Diseases and Treatments
- Invertebrate Immune Response Mechanisms
- Leprosy Research and Treatment
Infectious Disease Research Institute
2011-2023
Access to Advanced Health Institute
2022
Seattle University
2020
McMaster University
2000-2016
Chembio (United States)
2008-2010
Anandaban Hospital
2008
University of Michigan
2000
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...
A subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, multiple-antigen will likely essential. However, the cost to used developing countries must considered. We describe herein multiantigen candidate comprised antigens known protective animal models, dogs, recognized by humans immune visceral The polyprotein (KSAC) formulated with monophosphoryl lipid A,...
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...
Clinical and experimental studies have shown that estradiol (E2) confers protection against HIV other sexually transmitted infections. Here, we investigated the underlying mechanism. Better in E2-treated mice, immunized genital HSV-2, coincided with earlier recruitment higher proportions of Th1 Th17 effector cells vagina post-challenge, compared to placebo-treated controls. Vaginal APCs isolated from mice induced 10-fold responses, progesterone-treated, placebo-treated, estradiol-receptor...
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....
Abstract Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as antimalarial drug artemisinin and β-farnesene. One only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulated into an emulsion vaccine adjuvant to enhance immune responses licensed vaccines. However, overfishing depleting deep-sea populations, leading potential supply problems squalene. We chemically generated...
Leprosy can be a devastating chronic infection that causes nerve function impairment and associated disfigurement. Despite the recent reduction in number of registered worldwide leprosy cases as result widespread use multidrug therapy, new detected each year remains relatively stable. The diagnosis is currently based on appearance clinical signs requires expert clinical, well labor-intensive time-consuming laboratory or histological, evaluation. For purpose developing an effective, simple,...
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, with several million new cases detected each year. Current methods of diagnosis are time-consuming and/or expensive or have low level accuracy. Therefore, diagnostics urgently needed to address the global tuberculosis burden and improve control programs. Serological assays remain attractive for use in resource-limited settings because they simple, rapid, inexpensive offer possibility detecting often...
Infection with Leishmania parasites results in a range of clinical manifestations and outcomes, the most severe which is visceral leishmaniasis (VL). Vaccination will likely provide effective long-term control strategy, as large number vectors potential infectious reservoirs renders sustained interruption parasite transmission extremely difficult. Selection best vaccine complicated because, although several antigen candidates have been proposed, they emerged following production different...
Abstract The involvement of innate receptors that recognize pathogen- and danger-associated molecular patterns is critical to programming an effective adaptive immune response vaccination. synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) synergizes with the squalene oil-in-water emulsion (SE) formulation induce strong responses. Although signaling through MyD88 TIR domain–containing adapter inducing IFN-β are essential for GLA-SE activity, mechanisms underlying synergistic activity...
Abstract Designing modern vaccine adjuvants depends on understanding the cellular and molecular events that connect innate adaptive immune responses. The synthetic TLR4 agonist glycopyranosyl lipid adjuvant (GLA) formulated in a squalene-in-water emulsion (GLA-SE) augments both humoral responses to Ags. This is currently included several vaccines undergoing clinical evaluation including those for tuberculosis, leishmaniasis, influenza. Delineation of mechanisms activity will enable more...
Vaccine development for vector-borne pathogens may be accelerated through the use of relevant challenge models, as has been case malaria. Because demonstrated biological importance vector-derived molecules in establishing natural infections, incorporating models into vaccine strategies increase accuracy predicting efficacy under field conditions. Until recently, however, there was no model available evaluation candidates against visceral leishmaniasis. We previously that a candidate...
Female sex steroids, estradiol (E2) and progesterone (P4), play a key role in regulating immune responses women, including dendritic cell (DC) development, functions. Although the two hormones co-occur body of women throughout reproductive years, no studies have explored their complex combinatorial effects on DCs, given ability to regulate each other's actions. We examined murine bone marrow derived cells (BMDC) differentiation functions, presence wide range physiological concentrations...
Abstract The triggering Ag for inflammatory bowel disease and animal models of colitis is not known, but may include gut flora. Feeding OVA to DO11.10 mice with OVA-specific transgenic (Tg) TCR generates Ag-specific immunoregulatory CD4+ T cells (Treg) cells. We examined the ability oral Ag-induced Treg suppress cell-mediated in mice. SCID-bg given CD4+CD45RBhigh developed colitis, cotransferring CD45RBlowCD4+ prevented cell-induced absence OVA. induction prevention by cell subsets were...
Background The malaria parasite Plasmodium falciparum EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 F2 characterization of were studied using specific monoclonal antibodies (mAbs) against these domains. Methods Findings Five mAbs for or generated. Three potently blocked binding to erythrocytes, merozoite invasion...
The growing shift to subunit antigen vaccines underscores the need for adjuvants that can enhance magnitude and quality of immune response.
Amebiasis is a neglected tropical disease caused by Entamoeba histolytic a. Although the burden varies geographically, amebiasis estimated to account for some 55,000 deaths and millions of infections globally per year. Children travelers are among groups with greatest risk infection. There currently no licensed vaccines prevention amebiasis, although key immune correlates protection have been proposed from observational studies in humans. We previously described development liposomal...
Background Recognition of the importance dendritic cells (DC) in initiation T-cell–dependent immune responses has led to increasing interest methods for identification DC within circulation. We sought develop a flow cytometric method that would allow reliable enumeration absolute myeloid counts minimally manipulated blood samples. Methods Myeloid were identified by three-color staining whole leukocytes as discrete population mononuclear expressing high levels HLA-DR and CD33, yet having...
Many pathogens establish infection at mucosal surfaces such as the enteric pathogen Enterotoxigenic E. coli (ETEC). Thus, there is a pressing need for effective vaccination strategies that promote protective immunity surfaces. Toll-like receptor (TLR) ligands have been extensively developed vaccine adjuvants to systemic immunity, whereas attenuated bacterial toxins including cholera toxin and heat-labile (LT) initially immunity. Here we evaluate ability of TLR4 agonist second-generation...
Converting a vaccine into thermostable dry powder is advantageous as it reduces the resource burden linked with cold chain and provides flexibility in dosage administration through different routes. Such presentation may be especially useful development of towards respiratory infectious disease tuberculosis (TB). This study assesses immunogenicity protective efficacy spray-dried ID93+GLA-SE, promising TB candidate, against Mycobacterium (Mtb) murine model when administered via Four routes...
Abstract Little is understood about the earliest cytokine responses and role(s) of donor CD4 T cells in intestine during induced graft-vs-host reaction (GVHR). We investigated activation mucosal homing phenotype kinetics within associated lymphoid tissues early GVHR. Significant frequencies accumulated recipient Peyer’s patches (PP), mesenteric lymph nodes (MLN), lamina propria (LP), spleen (SP), first 9 days Many SP, MLN, LP expressed CD44 also de novo integrin α4β7 (LPAM-1). A large IFN-γ...
Enterotoxigenic E. coli (ETEC) is a leading cause of moderate-to-severe diarrhoea. ETEC colonizes the intestine through fimbrial tip adhesin colonization factors and produces heat-stable and/or heat-labile (LT) toxins, stimulating fluid electrolyte release to watery We reported that vaccine containing recombinant factor antigen (CfaEB) targeting I (CFA/I) an attenuated LT toxoid (dmLT) elicited mucosal systemic immune responses against both targets. Additionally, toll-like receptor 4 ligand...
With the recent exception of coronavirus disease 2019 (COVID-19), tuberculosis (TB) causes more deaths globally than any other infectious disease, and approximately 1/3 world's population is infected with Mycobacterium (Mtb). However, encouraging progress in TB vaccine development has been reported, 50% efficacy achieved Phase 2b clinical testing an adjuvanted subunit candidate. Nevertheless, current lead candidates require cold-chain transportation storage. In addition to temperature...