Thursday, October 23, 2014

The Public Demands An Ebola Vaccine With 100% Survival Rate - NOW!





As a survivor of cancer and a stock investor, I am well motivated to put cash towards companies making strides in curing it. Inovio came onto my radar a few years ago and I have watched this pharmaceutical company unfold like a flower. It is a wonder to watch! They are working on the new technology for medicine - vaccines for curing cancer and preventing viruses and drug-resistant bacteria (think e. coli, strep, HPV, HIV, Hep C, all strains of flu, pandemic flus, ebola, MERS, mosquito-born illnesses) and eventually autoimmune diseases, was an easy choice for investing. After due diligence, and being stunned by their research, scientists, board of directors, CEO, and plan to be a large pharma of the future of medicine, not based on the old-world way of throwing drugs at those who are weak and dying, but giving real options to heal themselves, I went in whole hog in support!


This interview with the CEO explains why their Ebola vaccine SynCon, is so ideal for this situation; it does not need to use the actual virus to produce, can be mass produced, doesn't need refrigeration, is mixed with water-not eggs, and can work on the various strains. 

How do DNA vaccines work? A very well versed person summed it up for the public in this wording - 


The immune system rests on two major pillars: the innate, general defense and the adaptive specialized defense. Both systems work closely together but they have different purposes and different ways in which they respond. Our innate immune systems give immediate defense against infection, and are found in all plant and animal life. The innate system is the evolutionarily older defense strategy. It is the main immune system found in plants, fungi, insects, and in primitive multicellular organisms. The system is not adaptable and does not change over the course of an individual's lifetime. 


There are three major armies in this line of defense. 
1) Soluble substances, which belong to the protein group, support the defense cells of the innate immune system. A total of nine different enzymes activate one another in a process similar to a chain reaction: one enzyme of the first stage alerts several enzymes of the second stage, each of which again activates several enzymes of the third stage, and so on. This process quickly makes the defense reaction a lot stronger, because the production of these protein substances increases in such large jumps (exponentially). 
2) White blood cells (WBC) are a major army in the innate immune system that defends the body from infection. They are known as leukocytes. Leukocytes are different from other cells of the body: they work like independent, single-celled organisms. They can move freely, and capture cell debris, foreign particles, or invading microorganisms. They are produced by blood-forming stem cells in the bone marrow. The innate leukocytes include: Natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells including macrophages, neutrophils and dendritic cells. They identify and eliminate pathogens that cause infection. 
3) So-called natural killer cells are the third important part of the innate immune system. They specialize in identifying cells that are infected by a virus or that have become tumorous. They do this by looking for changes in cell surfaces. If natural killer cells find cells with a changed surface, they dissolve them using cell poisons, also called cytotoxins.

The Dendritic cells (DC) are of special interest. They are phagocytic cells present in tissues that are in contact with the external environment, mainly the skin (where they are often called Langerhans cells), and the inner mucosal lining of the nose, lungs, stomach and intestines. Phagocyte means a cell, such as white blood cell that swallows (engulfs) and absorbs harmful organisms and other foreign bodies in the bloodstream and in tissues.

The active immune system really revolves around the battle between antigens and antibodies. The invading microbe or pathogen is called an antigen. It is regarded as a threat by the immune system and is capable of stimulating an immune response. Antigens are proteins that are found on the surface of the pathogen. Antigens are unique to that pathogen."Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens are identified as intruders and attacked by the immune system. Autoimmune disorders arise from the immune system reacting to its own antigens.

Antibodies are made available for germs outside the cells (in the blood and in body fluids). To eliminate pathogens that are inside the tissue, a cell-mediated immune response is necessary. Antibodies circulate in the blood stream and can appear anywhere throughout the body. If circulating antibodies come in contact with the target or antigen they were generated to fight, then the antibodies bind to the target. Depending on the antigen, the binding may impede the biological process causing the disease or may recruit macrophages to destroy the foreign substance. Antigenic molecules are normally large and they usually present several surface features that can act as points of interaction for specific antibodies. Any such distinct molecular feature constitutes an epitope. There are two broad purposes of antibodies. The first is a binding operation- bind to the antigen so that it can’t do whatever it’s doing to harm us. In the blood, this might take the form of binding a target bacteria so that it can’t infect any more cells. The second purpose of antibodies is to recruit other cells or proteins to an antigen so that those cells or proteins can eliminate the antigen.

A virus is a highly sophisticated parasite. It has no biosynthetic or metabolic apparatus of its own and can replicate (reproduce) only inside cells. Once inside cells, these pathogens are not accessible to antibodies. Antibodies can be eliminated only by the destruction or modification of the infected cells on which they depend. In the immune system, the T cell fulfills this role. But the immune defense system must be able to recognize the infected cells and the T cell must be specific for that antigen.

On the surface of the cell, there is a brief, coded system for signaling what is in the cell. There are pieces of molecules that camp like little families on the cell surface. The group of clumps may all be related to form a larger set. Genes are categorized into families based on shared nucleotide or protein sequences. If the genes of a gene family encode proteins, the term protein family is often used in an analogous manner to gene family. This extended gene family is a set of several similar gene clumps, formed by duplication of a single original gene, and generally with similar biochemical functions. A set of cell surface molecules encoded by a large gene family is called a major histocompatibility complex, or MHC.

Each MHC molecule camped on the cells surface displays a molecular fraction, called epitope, of a protein. The presented antigen can be either self or nonself. The MHC population in its entirety is like a meter indicating the balance of proteins within the cell.

Cells that become infected by a virus or cancer would typically signal the immune response for help by producing antigens on the surface. But, infected cells can be very adaptive at survival. They have hijacked the cells for their own reproduction, and they have learned to hide and compromise an immune response.

DNA immunization is used to efficiently stimulate humoral and cellular immune responses to protein antigens. Protein molecules—either a person’s own phenotype or of other biologic entities—are continually synthesized and degraded in a cell. Inovio’s synthetic DNA vaccines consist of DNA plasmids encoded to produce one or more antigens associated with a target pathogen (e.g. bacteria, virus or cancer). The plasmid DNA molecules encode pathogen antigens to induce a pathogen-specific immune response. As a carrier of genetic code, these DNA plasmids, which are circular pieces of DNA are made to be closely similar to the genome of the disease it is targeting. This means that they provide the ability for the immune system to be trained on the type of antigen it should be attacking. The antigens encoded in the DNA plasmids enter the cell by electroporation. The direct injection of genetic material into a living host causes some of its cells to produce the introduced gene products. It does not affect the DNA. After the plasmid delivers the DNA instructions into cells it is readily metabolized by the body so that concerns about long-term persistence of the DNA plasmids are minimized. Numerous human clinical studies have established that DNA plasmids have a favorable safety profile. After uptake of the plasmid, the protein is produced endogenously and intracellularly processed into small antigenic peptides. The protective immune peptides (i.e., epitopes) can then be transferred to the cell surface and activate T cells- the DNA plasmids work their way to the surface where they can send the signal that they are really cells that should be attacked by the body’s immune system.

Antigens inside a cell are bound to class I MHC (major histocompatiblity) molecules, and brought to the surface of the cell by the class I MHC molecule. Now the cells can be recognized by the T cell. MHC class I interacts with CD8 molecules on the surfaces of Cytotoxic T cells to mediate destruction of infected or malignant host cells like cancer. This all relates to what is termed cellular immunity.

MHC class II mediates establishment of specific immunity (also called acquired immunity or adaptive immunity) by interacting with CD4 molecules on surfaces of T helper cells (Th). Mature Th cells express the surface protein CD4 and are referred to as CD4+ T cells. CD4+ T cells are generally treated as having a pre-defined role as helper T cells within the immune system. For example, when an antigen presenting cell expresses an antigen on MHC class II, a CD4+ cell will aid those cells through a combination of cell to cell interactions and through cytokines.

A portion of the DNA vaccine is also taken up directly by the Antigen Presenting Cells and the encoded antigen can then be processed and presented endogenously (Humoural Immunity).The cells are now antigen presenting cells (APC’s). Antigen-loaded APCs travel to the draining lymph nodes, where they present peptide antigens to naïve T cells, thereby eliciting both humoral and cellular immune responses. Signaling from the APC directs T cells into particular subtypes. Helper T (TH) cells are critical to coordinating the activity of the immune response-I will elaborate on that below. The chemical messages they secrete (cytokines) stimulate the non-specific immune response to continue, and strengthen and boost appropriate specific responses. Helper T cells have sometimes been called the "conductors" of the immune system because they coordinate activity like the conductor of a symphony. They have also been called the "generals" of the immune system because they call up troops to go into battle.

The process that conveys antigens to the APC is highly efficient since DNA vaccines, which produce only very low levels of antigen, can induce all arms of the immune response. Plasmid DNA vaccines are particularly suited to induce CD8+ T cell responses because they express antigens intracellularly, introducing them directly into the MHC I antigen processing and presentation pathway.

T cells play an important role in immune system responses to pathogens and cancer- Dr. Kim thinks that they play the most important role. They are able to kill infected and abnormal cells or aid in activating different other cell types as part of an immune response. T-cells have many identical T-cell receptors (TCR) that cover their surface and can only bind to one shape of antigen. Now that the target cell has become “flagged” a T cell can recognize it. The antigen flag is a signal for a killer T-cell to let it know that this is a cell that must be destroyed. There are millions of T-cells, but each T-cell can fight only one type of virus. The vaccine has given instructions to the T-cell WHAT it should be targeting and killing. The T-killer cell is cytotoxic, which means it kills. They are also called T lymphocyte, CTL, or CD8+ T-cells or killer-T cells. DNA vaccines are able to induce strong CTL responses.

T-cells have many identical T-cell receptors (TCRs) that cover their surface and can only bind to one shape of antigen. The killer T-cells now have the key, the specific TCRs for the antigen that is sitting like a unique lock on the targeted cell.
TCRs go through a developmental process in which they recognize an MHC class I-presented antigen (CD8), or an MHC class II-presented antigen (CD4). It is the CD8+ T-cells that will mature and go on to become cytotoxic T cells following their activation with a class I-restricted antigen (MHC I).

When the perfectly shaped virus antigen on an infected cell (the key) fits into the Killer T-cell receptor (the lock), the T-cell releases perforin and cytotoxins. Perforin first makes a pore, or hole, in membrane of the infected cell. Cytotoxins go directly inside the cell through this pore, destroying it and any viruses inside. That is why Killer T-cells are also called Cytotoxic T-cells. The pieces of destroyed cells and viruses are then cleaned up by macrophages. The elimination of infected cells without the destruction of healthy tissue requires the cytotoxic mechanisms of CD8 T cells to be both powerful and accurately targeted. Cytotoxic T cells kill their targets by programming them to undergo apoptosis (the death of the cell). CTL killing requires cell contact. CTL are triggered to kill when they recognize the target antigen associated with a cell surface MHC molecule. Adjacent cells lacking the appropriate target MHC-antigen are not affected and each CTL is capable of killing sequentially numerous target cells.

Helper T cells (Th) become activated when they are presented with antigens by MHC class II molecules, which are also expressed on the surface of antigen-presenting cells (APCs). After a Killer T-cell finds and destroys an infected cell, a Helper T-cell message tells the Killer T-cell to copy itself, making an army of Killer T-cells. Since only T-cells that can fight the invading virus are copied, your body saves energy and is still very good at killing the virus. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. These cells can differentiate into one of several subtypes, including which secrete different cytokines to facilitate a different type of immune response. Regulatory T cells (Treg cells) are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction

Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their known antigen to provide the immune system with "memory" against past infections.
One of these different subtypes of T cells are T helper cells. They mature from naive T cells during an immune response after antigen stimulation.

Different lineages of T helper cells secrete different sets of characteristic cytokines helping to orchestrate the immune response and aiding in activating other cell types of innate and adaptive immunity. The development of T helper cells into different lineages, depends on the cytokine environment that induces different master regulators.

Compared to other types of vaccines (e.g., live attenuated or killed whole organism vaccines, and subunit vaccine), DNA vaccines are safe, easy to prepare and store, and cost effective. In addition, DNA vaccines allow for focused immunity on the antigen of interest and have the ability to induce natural, long-lasting, and varied immune responses in vivo.


Monoclonal antibodies (mAb) were a transformational scientific innovation designed to enhance the immune system's ability to regulate cell functions. They are designed to bind to a very specific epitope (area) of an antigen or cell surface target and can bind to almost any selected target. mAbs have the unique ability to alert the immune system to attack and kill specific cancer cells (as in the case of Yervoy®) or block certain biochemical pathways (such as those leading to rheumatoid arthritis, as in the case of Remicade®). However, mAb technology has limitations. Delivered by passive administration, meaning they are manufactured outside the body, mAbs typically require costly large-scale laboratory development and production. Additional limitations include the necessity for repeat administrations and their limited duration of in vivo potency.
The paradigm shift of Inovio's technology is that the DNA for a monoclonal antibody is encoded in a DNA plasmid, delivered directly into cells of the body using electroporation, and the mAbs are "manufactured" by these cells. Using this patent-protected approach, Inovio previously published that a single administration of a highly optimized DNA-based monoclonal antibody targeting HIV virus in mice generated antibody molecules in the bloodstream possessing desirable functional activity including high antigen-binding and HIV-neutralization capabilities against diverse strains of HIV viruses." There most recent publication new work further demonstrated the capability of this technology using a CHIKV challenge model.



Let's look at RSV infections (respiratory syntial virus often caught by the young and resulting in cough and breathing difficulties).  

Palivizumab ("Synagis") has been shown to be a remarkably safe (causing almost no side effects or adverse reactions) and reasonably effective (reducing the incidence of RSV infections in susceptible persons to about half of what would be expected without use of the drug during a typical winter season). It sounds like a win-win situation. What’s the problem?Synagis™ must be given monthly during the season; the length of the RSV season varies by location but is typically four to six months. Each monthly treatment has a cost of $1500 to $2000 for an annual cost of about $9000 per patient. The wholesale price of Synagis™ is $1416.48 for a single-dose 100 mg vial that will treat a 15-pound child.


MedImmune's process is costly and has a short life once injected. Inovio’s DNA based vaccine technology would allow mAbs to be produced at a cheaper cost and along with electroporation (Inovio's specially patented injection device) produce a much longer lasting effect that would enhance the efficacy of the drug itself.

The company just got a DARPA grant for 12 million dollars to tackle issues like drug-resistance. 

The collaboration will focus on three disease areas – influenza virus, Pseudomonas aeruginosa and Staphylococcus aureus. An estimated 51,000 healthcare-associated P. aeruginosa infections occur in the United States each year. More than 6,000 (13%) of these are multidrug-resistant, with roughly 400 deaths per year attributed to these infections. Multidrug-resistant Pseudomonas was given a threat level of serious threat in the CDC AR Threat report

"The project proposes ... to provide a platform to rapidly protect people against emerging infections through the development of novel synthetic antibodies produced by the patients themselves."

- Here's Inovio

About Inovio Pharmaceutical (INO): Inovio is a small cap, mid stage, biotechnology company that engages in the the research and development of SynCon DNA Vaccines. The arena of DNA Vaccines is cutting edge and has the possibility of changing modern medicine as we know it.

Management / Advisors: The management of Inovio Pharmaceuticals (INO) is top notch, many of the members have been management or involved with other large Biotech and Pharmaceutical companies. Below is a list of some of the management assets INO posses, not all are listed and not all of the credentials are listed for each member, this is just a quick run down. All information was pulled from www.inovio.com


1. Dr. Joseph Kim, PhD, CEO

Dr. Kim received a Bachelors of Science for chemical engineering and Economics from MIT, a MBA in Finance from the Wharton School of Business, and a PhD in biochemical engineering from the University of Pennsylvania.

Dr. Kim was a senior vaccine developer for Merck before he started VGX with Dr. Weiner, his mentor from U.Penn. Dr. Weiner is considered the father of DNA vaccines.


2. NIRANJAN Y. SARDESAI, PhD, COO

Dr. Sardesai received a Doctor of Philosophy degree in Chemistry from the California Institute of Technology and a Master of Business Administration from the Wharton School of the University of Pennsylvania, where he was the recipient of the Shils-Zeidman Award in Entrepreneurship. He completed fellowships at Scripps Research Institute and the Massachusetts Institute of Technology (MIT). Dr. Sardesai received his Bachelor and Master of Science degrees in Chemistry from the Indian Institute of Technology, Bombay.

Dr Sardesai served as Director of Research and Development at Fujirebio Diagnostics, Inc., where he oversaw research and development and expansion of the company’s oncology portfolio. Products developed under his leadership include groundbreaking new tests for mesothelioma (MESOMARK™), bladder cancer and a multi-marker test for ovarian cancer.

3. MARK L. BAGARAZZI, MD, Chief Medical Officer

Dr. Bagarazzi over seen the product and regulatory development of products such as Zostavax and RotaTeq while with Merk.

4. David B. Weiner, PhD, Chairman INO Scientific Board

Dr. Weiner is the Co-Founder of VGX and considered the father of DNA Vaccines.

5. Other members to read about:

Management: Peter Kies CFO, Stephen Kemmerrer VP of Engineering Operations, Thomas Kim Esq Legal and Corporate Secretary

Board of Directors: Avtar Dhillon, M.D., Simon X. Benito, Angel Cabrera, Ph.D., Morton Collins, Ph.D., Adel Mahmoud, Ph.D.

Scientific Advisory Board: Thomas S. Edgington, M.D., Anthony Ford-Hutchinson, Ph.D., Philip D. Greenberg, M.D., Stanley A. Plotkin, M.D.


Pipeline:  The company has a huge pipeline including vaccine trials for HPV-related dysplasia and cervical cancer, head and neck cancers related to HPV, Hep C, HIV, universal flu vaccine, malaria, prostate cancer, MERS, ebola, and mosquito-related diseases.

Ebola vaccine: The ebola vaccine had a 100% survival rate without illness in animal testing and is ready now for human testing starting in January. But, is January too late to for the people in West Africa and the health care workers who treat them? Dr. Kim has assured that the vaccine can be mass produced and expediently, shipped without refrigeration. This seems to me to be the time to fast-track such a protective vaccine.

The public is demanding answers now and with the death rate being over 70% for ebola, nearly anyone faced with possible exposure would agree, give me the shot. Now. 

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