A5023265367- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- CAR-T cell therapy research
- Transgenic Plants and Applications
- Herpesvirus Infections and Treatments
- Cervical Cancer and HPV Research
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Cancer Immunotherapy and Biomarkers
- Viral Infections and Vectors
- Microbial Inactivation Methods
- Viral Infections and Outbreaks Research
- Immune Response and Inflammation
- Virology and Viral Diseases
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
University of Pennsylvania
2013-2025
The Wistar Institute
2016-2025
MedStar Georgetown University Hospital
2023
Georgetown University
2023
Hospital of the University of Pennsylvania
1990-2022
Icahn School of Medicine at Mount Sinai
2022
ORCID
2021
Holy Cross University
2021
Jan Kochanowski University
2021
Inovio Pharmaceuticals (United States)
2010-2020
Protecting Against a Barrier Breach In order to coexist peacefully, “firewall” exists that keeps the commensal bacteria reside in our intestines and associated lymphoid tissue contained. Several diseases infections, however, lead breach this barrier, which leads chronic inflammation pathology. Sonnenberg et al. (p. 1321 ) found mice, innate cells (ILCs) are critically important for anatomical containment of an interleukin-22 (IL-22)–dependent manner. ILC depletion or blockade IL-22 led loss...
Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue vivo have been developed. In theory, gene inoculation should result the production of antigenic proteins a natural form immunized host. Here we present use such technique for mice with human immunodeficiency virus type 1 (HIV-1) envelope construct (pM160). Mice were injected intramuscularly pM160 and subsequently analyzed their anti-HIV immune responses. Antisera collected from inoculated...
A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety host immune response in 15 asymptomatic HIV-infected patients who were not using antiviral drugs had CD4+ lymphocyte counts of ⩾500 per microliter blood. Successive groups received three doses (30, 100, or 300 µg) at 10-week intervals a dose-escalation trial. Vaccine administration induced no local systemic reactions, laboratory abnormalities detected. Specifically, patient...
The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of disease. We have previously engineered a synthetic DNA targeting MERS Spike (S) protein, major surface antigen coronaviruses, which currently in clinical study. Here we build on prior experience generate DNA-based candidate S protein. construct, INO-4800, results robust expression protein...
CD8 + T cells with cytolytic activity are induced after therapeutic human papillomavirus vaccination in humans.
A vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA (INO-4800) targeting full length spike antigen are described.INO-4800 was evaluated in two groups 20 participants, receiving either 1.0 mg or 2.0 intradermally followed CELLECTRA® EP at 0 4 weeks. Thirty-nine subjects completed both doses; one subject group discontinued trial participation prior to second dose. ClinicalTrials.gov identifier: NCT04336410.The median age 34.5, 55% (22/40) were...
Abstract Cross-presentation is a critical function of dendritic cells (DCs) required for induction antitumor immune responses and success cancer immunotherapy. It established that tumor-associated DCs are defective in their ability to cross-present antigens. However, the mechanisms driving these defects still unknown. We find impaired cross-presentation largely associated with defect trafficking peptide–MHC class I (pMHC) complexes cell surface. tumor-bearing hosts accumulate lipid bodies...
A consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge.
Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There no approved vaccines against ZIKV infection.
Anti-PD-1 therapy is used as a front-line treatment for many cancers, but mechanistic insight into this resistance still lacking. Here we generate humanized (Hu)-mouse melanoma model by injecting fetal liver-derived CD34+ cells and implanting autologous thymus in immune-deficient NOD-scid IL2Rγnull (NSG) mice. Reconstituted Hu-mice are challenged with HLA-matched melanomas treated anti-PD-1, which results restricted tumor growth not complete regression. Tumor RNA-seq, multiplexed imaging...
Abstract Programmed cell death protein 1 (PD-1) inhibitors have modest efficacy as a monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) may enhance responses to PD-1 through the induction of tumor-specific immunity. We present results from single-arm, open-label, phase 1/2 study DNA plasmid PTCV (GNOS-PV02) encoding up 40 neoantigens coadministered with plasmid-encoded interleukin-12 plus pembrolizumab patients advanced HCC previously treated...
In the absence of cell surface cancer-specific antigens, immunotherapies such as chimeric antigen receptor (CAR) T cells, monoclonal antibodies, or bispecific engagers typically target lineage antigens. Currently, are individually designed and tested for each disease. This approach is inefficient limited to a few antigens which on-target/off-tumor toxicities clinically tolerated. Here, we sought develop universal CAR therapy blood cancers directed against pan-leukocyte marker CD45. To...
Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions demonstrate immunogenicity safety preclinical clinical development. Optimized vaccines generate protective immunity (according WHO defined thresholds) at doses up 1,000,000-fold lower than female...
Abstract Recent studies support the importance of investigating a DNA vaccination approach for immunologic control HIV-1. In this regard, it may be important to specifically engineer immune responses in order improve on first generation vaccine attempts. Especially HIV, induction cell-mediated immunity an feature any candidate vaccine. attempt vivo enhancement cellular response and direct Ag-dependent from Th2 Th1 type, we investigated role codelivery genes IL-12 granulocyte-macrophage-CSF...
DNA vaccination, or genetic immunization, is a novel vaccine technology that has great potential for reducing infectious disease and cancer-induced morbidity mortality worldwide. Since their inception, vaccines have been used to stimulate protective immunity against many pathogens, malignancies, autoimmune disorders in animal models. Plasmid encoding polypeptide protein antigen introduced into host where it enters cells serves as an epigenetic template the high-efficiency translation of its...