A5071608389- Cervical Cancer and HPV Research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Hepatitis B Virus Studies
- Head and Neck Cancer Studies
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Outbreaks Research
- RNA Interference and Gene Delivery
- Prostate Cancer Treatment and Research
- Microbial Inactivation Methods
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Vaccine Coverage and Hesitancy
- Colorectal and Anal Carcinomas
- Animal Virus Infections Studies
- Toxin Mechanisms and Immunotoxins
- Cytomegalovirus and herpesvirus research
- Reproductive tract infections research
- SARS-CoV-2 detection and testing
- Immune Cell Function and Interaction
- Diphtheria, Corynebacterium, and Tetanus
- Bladder and Urothelial Cancer Treatments
- Viral Infections and Vectors
- Virology and Viral Diseases
- Immune responses and vaccinations
Merck & Co., Inc., Rahway, NJ, USA (United States)
2024
Inovio Pharmaceuticals (United States)
2014-2023
University of California, San Diego
2011-2019
University of Pennsylvania
2009-2012
Philadelphia University
2012
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...
A consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge.
Abstract Significant concerns have been raised owing to the rapid global spread of infection and disease caused by mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing exposure risk for this virus. Associated with is a dramatic increase in cases microcephaly additional congenital abnormalities infants ZIKV-infected mothers, as well rise occurrence Guillain Barre’ syndrome infected adults. Importantly, there are no licensed...
Abstract Purpose: Clinical responses with programmed death (PD-1) receptor–directed antibodies occur in about 20% of patients advanced head and neck squamous cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins HPV16/18, are attractive targets for therapeutic immunization offer an immune activation strategy that may be complementary to PD-1 inhibition. Patients Methods: We report phase Ib/II safety, tolerability, immunogenicity results immunotherapy MEDI0457 (DNA targeting...
Abstract Background Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2–8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA generates protection from lethal EBOV challenge small animals nonhuman primates, we performed a clinical study evaluate both intramuscular (IM) novel intradermal (ID) delivery. Methods Two candidates (INO-4201 INO-4202) targeting the glycoprotein (GP) were evaluated for safety,...
Abstract Background Additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines that are safe and effective as primary boosters remain urgently needed to combat the disease 2019 (COVID-19) pandemic. We describe safety durability of immune responses following doses a homologous booster dose an investigational DNA vaccine (INO-4800) targeting full-length spike antigen. Methods Three dosage strengths INO-4800 (0.5 mg, 1.0 2.0 mg) were evaluated in 120 age-stratified healthy...
Abstract Background Vaccines against SARS-CoV-2 are still urgently needed as only 5% of the global population has been vaccinated. Here we report safety and immunogenicity a DNA vaccine (INO-4800) targeting full-length Spike antigen when given to adults at high-risk exposure. Methods INO-4800 was evaluated in 401 participants randomized 3:3:1:1 ratio receive either (1 mg or 2 dose) placebo injections) intradermally (ID) followed by electroporation (EP) using CELLECTRA® 2000 Days 0 28....
Background Human telomerase reverse transcriptase (hTERT) is frequently classified as a ‘universal’ tumor associated antigen due to its expression in vast number of cancers. We evaluated plasmid DNA-encoded hTERT an immunotherapy across nine cancer types. Methods A phase 1 clinical trial was conducted adult patients with no evidence disease following definitive surgery and standard therapy, who were at high risk relapse. Plasmid DNA encoding one two variants (INO-1400 or INO-1401) without...
Purpose: As previously reported, treatment of high-grade cervical dysplasia with VGX-3100 resulted in complete histopathologic regression (CR) concomitant elimination HPV16/18 infection 40.0% VGX-3100-treated patients compared only 14.3% placebo recipients a randomized phase IIb study. Here, we identify clinical and immunologic characteristics that either predicted or correlated therapeutic benefit from to parameters might guide decision-making for this disease.Experimental Design: We...
We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for treatment Human Papillomavirus (HPV)16/18-positive CIN2/3 in phase 1 clinical trial. Here, we report on ability to boost immune responses with an additional dose VGX-3100. Patients completing our initial trial were offered enrollment into follow consisting single Data show both cellular and humoral could be augmented above pre-boost levels, including induction interferon (IFN)γ production,...
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...
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...
ABSTRACT To date, no vaccine that is safe and effective against herpes simplex virus 2 (HSV-2) disease has been licensed. In this study, we evaluated a DNA prime-formalin-inactivated-HSV-2 (FI-HSV2) boost approach in the guinea pig model of acute recurrent HSV-2 genital disease. Five groups pigs were immunized intravaginally challenged with HSV-2. Two primed plasmid DNAs encoding secreted form glycoprotein D2 (gD2t) together two genes required for viral replication, either helicase (UL5)...
The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown be significantly enhanced by addition electroporation (EP) treatment protocol. Principally, EP increases transfection plasmid (pDNA) into resident cells. In increasing levels in vivo transfection, physical insult induced is associated with activation innate pathways which are believed mediate an adjuvant effect, further enhancing vaccine responses. We investigated possible mechanisms this...
A significant hurdle in vaccine development for many infectious pathogens is the ability to generate appropriate immune responses at portal of entry, namely mucosal sites. The approaches resulting secretory IgA and cellular against target great interest general, requires live viral infection Using HIV-1 influenza antigens as models, we report here that a novel systemically administered DNA vaccination strategy utilizing co-delivery specific chemokine molecular adjuvant CCL25 (TECK) can...
Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, an effective, safe RSV vaccine remains unmet need. Here we assess novel vaccination strategy based on intradermal delivery of SynCon® DNA-based encoding engineered RSV-F antigen using surface electroporation device (SEP) to target epidermal cells, clinically relevant experimental models. We demonstrate ability this elicit robust immune responses. Importantly complete resistance...
: Background: Recurrent respiratory papillomatosis (RRP) is a rare disorder characterized by the generation of papillomas aerodigestive tract, usually associated with human papilloma virus (HPV) subtypes 6, 11. INO-3106 DNA plasmid-based immunotherapy targeting E6 and E7 proteins HPV6, in order to create robust immune T cell response.Testing INO-3016 animal models confirmed immunogenicity DNA-based therapy. A single-site open-label Phase 1 study was initiated for patients HPV6-positive RRP....
The management of men with prostate cancer (PCa) biochemical recurrence following local definitive therapy remains controversial. Early use androgen deprivation (ADT) leads to significant side effects. Developing an alternative, clinically effective, and well-tolerated unmet clinical need. INO-5150 is a synthetic DNA that includes plasmids encoding for prostate-specific antigen (PSA) membrane (PSMA), INO-9012 plasmid interleukin-12 (IL-12). This phase 1/2, open-label, multi-center study...
Plasmid-encoded DNA vaccines appear to be a safe and effective method for delivering antigen; however, the immunogenicity of such is often suboptimal. Cytokine adjuvants including interleukin (IL)-12, RANTES, granulocyte-macrophage colony-stimulating factor, IL-15, others have been used augment immune response against vaccines. In particular, IL-15 binds unique high-affinity receptor, IL-15Rα; trans-presented CD8+ T cells expressing common βγ chain; has shown play role in generation,...