A5075430149- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- HIV Research and Treatment
- IL-33, ST2, and ILC Pathways
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Transgenic Plants and Applications
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Ubiquitin and proteasome pathways
- vaccines and immunoinformatics approaches
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Nursing education and management
- Prostate Cancer Treatment and Research
- Viral Infections and Outbreaks Research
- interferon and immune responses
- Animal Virus Infections Studies
- Respiratory viral infections research
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- Nanoplatforms for cancer theranostics
Princess Alexandra Hospital
2022-2024
Inovio Pharmaceuticals (United States)
2014-2023
Central Queensland University
2022-2023
The Wistar Institute
2016-2019
Pacific University Oregon
2019
University of Pennsylvania
2013-2017
Ministry of Food and Drug Safety
2014
Philadelphia University
2013
Ashland University
2013
A consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge.
The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of genomes accumulate in infected cells potently trigger the sustained activation transcription factors IRF3 and NF-κB production type I IFNs through a mechanism independent IFN signaling. We demonstrate these defective (DVGs) are generated naturally during respiratory infections vivo even mice lacking receptor, their appearance coincides with...
Studies of interleukin (IL)-33 reveal a number pleiotropic properties. Here, we report that IL-33 has immunoadjuvant effects in human papilloma virus (HPV)-associated model for cancer immunotherapy where cell-mediated immunity is critical protection. Two biologically active isoforms exist are full-length or mature, but the ability either isoform to function as vaccine adjuvant influences CD4 T helper 1 CD8 T-cell immune responses not defined. We showed both capable enhancing potent...
Purpose: Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts and an interesting target for cancer immune therapy, with prior studies indicating a potential to affect the tumor stroma. Our aim was extend this earlier work through development of novel FAP immunogen improved capacity break tolerance use combination antigen vaccines.Experimental Design: We used synthetic consensus (SynCon) sequence approach provide MHC class II help support breaking tolerance....
Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive administration has limitations, including the necessity purification multiple injections efficacy. is associated with a lag phase before generation of immunity. Novel approaches reported here utilize benefits both methods rapid effective immunity.A novel antibody-based prophylaxis/therapy entailing electroporation-mediated delivery synthetic DNA plasmids encoding biologically active...
The impact of broad-spectrum antibiotics on antimicrobial resistance and disruption the beneficial microbiome compels urgent investigation bacteria-specific approaches such as antibody-based strategies. Among these, DNA-delivered monoclonal antibodies (DMAbs), produced by muscle cells in vivo, potentially allow prevention or treatment bacterial infections circumventing some hurdles protein IgG delivery. Here, we optimize consisting two potent human clones, including a non-natural bispecific...
Abstract Antibody-based immune therapies targeting the T-cell checkpoint molecules CTLA-4 and PD-1 have affected cancer therapy. However, this therapy requires complex manufacturing frequent dosing, limiting global use of treatment. Here, we focused on development a DNA-encoded monoclonal antibody (DMAb) approach for delivery anti–CTLA-4 antibodies in vivo. With technology, engineered formulated DMAb plasmids encoding IgG inserts were directly injected into muscle delivered intracellularly...
Abstract Nanotechnologies are considered to be of growing importance the vaccine field. Through decoration immunogens on multivalent nanoparticles, designed nanovaccines can elicit improved humoral immunity. However, significant practical and monetary challenges in large‐scale production have impeded their widespread clinical translation. Here, an alternative approach is illustrated integrating computational protein modeling adaptive electroporation‐mediated synthetic DNA delivery, thus...
Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations therapies against influenza is pathogenic diversity generated by shift drift. simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing drugs seasonal pandemic outbreaks. We engineered synthetic plasmid DNA encode two novel broadly monoclonal antibodies targeting B....
Monoclonal antibody preparations have demonstrated considerable clinical utility in the treatment of specific malignancies, as well inflammatory and infectious diseases. Antibodies are conventionally delivered by passive administration, typically requiring costly large-scale laboratory development production. Additional limitations include necessity for repeat administrations, length vivo potency. Therefore, methods to generate therapeutic antibodies like molecules vivo, distinct from an...
ISG15 is an ubiquitin-like protein induced by type I interferon associated with antiviral activity. also secreted and known to function as immunomodulatory molecule. However, ISG15's role in influencing the adaptive CD8 T-cell responses has not been studied. Here, we demonstrate efficacy of a vaccine adjuvant, inducing human papilloma virus (HPV) E7-specific IFNγ well percentage polyfunctional, cytolytic, effector responses. Vaccination conferred remarkable control and/or regression...
Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development a IgG1 DMAb EBOV-GP mouse model. Using this approach, show that DMAb-11 DMAb-34 exhibit functional molecular profiles comparable recombinant mAb, have wide...
Specific antibody therapy, including mAbs and bispecific T cell engagers (BiTEs), are important new tools for cancer immunotherapy. However, these approaches slow to develop may be limited in their production, thus restricting the patients who can access treatments. BiTEs exhibit a particularly short half-life difficult production. The development of an approach allowing simplified development, delivery, vivo production would advance. Here we describe designed synthetic DNA plasmid, which...
BACKGROUNDHVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability, and immunogenicity of PENNVAX-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) intramuscular (IM) electroporation (EP) in healthy, HIV-uninfected adults. The study tested whether delivered ID/EP at one-fifth dose could elicit equivalent immune responses to delivery IM/EP inclusion pIL-12 provided additional benefit.METHODSParticipants...
Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and likely an important therapeutic target for the treatment of carcinoma. Current immunotherapy approaches to PSMA include peptide, cell, vector or DNA-based vaccines as well passive administration PSMA-specific monoclonal antibodies (mAb). Conventional mAb has numerous logistical practical limitations, including production costs a requirement frequent dosing due short serum half-life. In this...
Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially multiantibody deliveries, long infusion times, production issues could limit use of these bNAbs when deployed, globally affecting their application. Here, we...
Abstract Background There remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations are unable receive live-attenuated or viral vector vaccines. Methods We designed novel synthetic glycoprotein (EBOV-GP) DNA vaccines as a strategy expand protective breadth against diverse EBOV strains evaluated the impact of dosing route administration on protection lethal EBOV-Makona challenge in...
Cytolytic T cells (CTL) play a pivotal role in surveillance against tumors. Induction of CTL responses by vaccination may be challenging, as it requires direct transduction target or special adjuvants to promote cross-presentation. Here, we observed induction robust through electroporation-facilitated, DNA-launched nanoparticle (DLnano-vaccines). Electroporation was mediate transient tissue apoptosis and macrophage infiltration, which were deemed essential the CTLs DLnano-vaccines systemic...
An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs), and elicitation antibody-dependent cellular cytotoxicity (ADCC). Previously, we demonstrated HIV/SIV immune responses in macaques humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP). However, ability this improved approach to prime for relevant antibody has not been previously studied. Here, investigate immunogenicity...
Vaccination remains one of the greatest medical breakthroughs in human history and has resulted near eradication many formerly lethal diseases countries, including complete smallpox. However, there remain a number for which are no or only partially effective vaccines. There numerous hurdles vaccine development, knowing appropriate immune response to target is them.