(Inovio) DNA and Protein Co-Immunization Improves the Magnitude and Longevity of Humoral Immune Responses in Macaques

Abstract 3/13/2014

We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.

Link For Full Abstract

About the Authors

Rashmi Jalah, Viraj Kulkarni, Candido Alicea, Barbara K. Felber

Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America

Vainav Patel, Margherita Rosati, Jenifer Bear, Antonio Valentin, George N. Pavlakis

Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America

Lei Yu, Yongjun Guan

Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America

Xiaoying Shen, Georgia D. Tomaras

Duke Human Vaccine Institute and Departments of Surgery and Immunology, Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America

Celia LaBranche, David C. Montefiori

Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States of America

Rajasekhar Prattipati, Abraham Pinter

Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America

Julian Bess Jr, Jeffrey D. Lifson

AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America

Steven G. Reed

Infectious Disease Research Institute, Seattle, Washington, United States of America

Niranjan Y. Sardesai

Inovio Pharmaceuticals, Inc., Blue Bell, Pennsylvania, United States of America

David J. Venzon

Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America

Inovio VGX-1027

VGX™-1027 anti-inflammatory drug

VGX™-1027 is an orally administered, small molecule drug for inflammatory diseases. A novel inhibitor of pro-inflammatory responses including TNF-alpha, this drug has demonstrated preclinical efficacy against Crohn’s disease and colitis, rheumatoid arthritis (RA), and Type 1 diabetes (T1D).

VGX-1027 has completed a phase I single-ascending dose, double-blind study in healthy volunteers in which the compound was generally well-tolerated. In keeping with its focus on its synthetic vaccine technology, Inovio plans to out-license this compound.

Inflammatory bowel disease is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract. The two most common inflammatory bowel diseases are ulcerative colitis and Crohn’s disease. The Centers for Disease Control estimates that as many as 1.4 million persons in the United States suffer from these diseases.

There is no known pharmaceutical or surgical cure for inflammatory bowel diseases. Current treatment includes corticosteroids, antibiotics and new biologics and immune modifiers that mitigate symptoms but do not prevent or cure the disease.

In the U.S. alone, 1.3 million people suffer from RA according to the National Institute of Arthritis and Musculoskeletal Skin Diseases. With significant unmet clinical need and the progressive introduction of higher value and more effective biopharmaceuticals, the rheumatoid arthritis market is expected to more than double in value to $27 billion by 2015. Type 1 diabetes (T1D), which can be fatal if untreated, usually strikes children and young adults, although it can strike at any age. In adults, T1D accounts for 5 to 10 percent (0.9 million -1.8 million people) of all diagnosed cases of diabetes in the U.S. alone. Risk factors for T1D may be autoimmune, genetic, or environmental. No known way to prevent type 1 diabetes exists.

Source-Inovio

By following the link to Inovio's website you can find four abstracts dating from 2007-2008. Information since has been very been limited. Inovio's CEO has been quite over the last few years in regards to clinical work concerning VGX-1027, failing to mentioning the clinical work in any of the company's investor conference presentations. I will note Inovio has a broad pipeline preclinical and clinical and not all data is released via PR update, many studies can be found on pubmed or in medical journals online.

Below I have listed so the most recent updates for VGX-1027

1) March 26th, 2009-VGX Pharmaceuticals Oral Inflammatory Drug Safe In Phase 1 Study

Link 

2) July 13th, 2012- Therapeutic Potential of Nitric Oxide -Modified Drugs In Colon Cancer Cells

Link

3) October 24th, 2013 Compounds Having Immunomodulator Activity- Patent (WO2013158794A1)

Link

4) February 14th, 2014 Newest Publication for VGX 1027 

Link

Inovio AACR Conference April 5-9, 2014 San Diego

Presentation of abstract

Tuesday April 8th 2014

Immunoadjuvant ISG15 enhances human papillomavirus

Author- Inovio Pharmaceuticals

Link To Conference Info

The deadline for submission of late-breaking abstracts was Monday, January 27. Abstracts detailing highly significant and timely findings in any area of cancer research that were not available at the time of the regular abstract deadline were considered by the AACR Annual Meeting Program Committee for presentation at the AACR Annual Meeting 2014. Only those abstracts that were deemed to be of high scientific priority have been accepted. A special subcommittee of the Program Committee evaluated the merit of late-breaking abstracts. Each late-breaking abstract must have been sponsored by an AACR member.

Authors who submitted abstracts confirm that they have not previously published these data, that they have not previously presented them at a large national annual scientific meeting, and that they are not planning to present or publish them prior to the dates of the AACR Annual Meeting 2014. Each abstract should have contained: (a) an introductory sentence indicating the purposes of the study; (b) a brief description of pertinent experimental procedures; (c) a summary of the new, unpublished data; and (d) a statement of the conclusions. Authors must accept sole responsibility for the statements in their abstracts. Abstract submitters were asked to carefully proofread to avoid errors in the published literature and to use American English spelling throughout. For more information regarding American English spelling, please refer to Scientific Style and Format:

The latest Inovio abstracts (INO)

Alarmin IL-33 Acts as an Immunoadjuvant To Enhance Antigen-Specific Tumor Immunity 

March 5th 2014 ahead of print- Inovio Pharmaceuticals

Link to new abstract   


Vaccine Technology IV:An ECI Conference

Feb 25th 2014 - ahead of print Inovio Pharmaceuticals

Link to new abstract  

INOVIO WILL BE REPRESENTED AT THE CONFERENCE- IMMUNOPOTENTIATORS IN MODERN VACCINES 7-9 May 2014, Sao Rafael Atlantic Hotel, Albufeira, Algarve, Portugal

Inovio will be included in the special poster session of the conference. Stand by for more details and further updates on INO's presence at the conference as they become available.

The IMV conference series offers a regular update on the developments/issues surrounding ‘immunopotentiators for modern vaccines’ and is a vital aspect of the
growth of this important area of vaccinology.
IMV 2014 will once again offer an international forum to review the current state of research and developments/applications of immunopotentiators/adjuvants for modern
vaccines and associated vaccine programmes/strategies. IMV 2014 will be of interest to researchers involved in determining the mechanisms of adjuvant function and
responses and optimising these responses, manufacturers of biologicals, those involved in the manufacture/licensing of injectable biologicals, and those interested in the
control of infectious and non/infectious diseases

conference link

INOVIO'S UP COMING CONFERENCE (INO)

World Vaccine Congress 2014 
Date- March 24-26, 2014 Location- Washington D.C.

Inovio's presentation's (3/25/2014) Visit the website to see full conference program, in addition Inovio has been nominated for six awards this year by the world vaccine congress voting can also be done by following the link below.


World Vaccine Congress Website