Interviewer: Can you describe ViRexx Medical’s Chimigen
Dr. Rajan George: Chimigen therapeutic vaccine is used to produce immune responses in a host against infections which are difficult to produce immune responses, by targeting the vaccine to dendritic cells. The Chimigen platform can be extended to develop therapies for difficult-to-treat chronic infectious diseases.
Interviewer: Does that mean the Chimigen platform can be used to treat any infectious disease?
Dr. Rajan George: Yes, except in cases where the immune system is non-functional, as in the case of HIV.The Chimigen platform can be used to produce either a therapeutic vaccine or a prophylactic vaccine. This depends on the disease target and the antigen plugged into the platform. Some antigens have a use in treating infection, while others have a use in preventing an infection. Either one would be targeted to the dendritic cells. The therapeutic vaccine generates a cytotoxic T cell response. A prophylactic vaccine would generate a B cell response and antibody production.
Interviewer: From the way you’ve described the Chimigen
Dr. Rajan George: We should be able to use this platform for cancer therapy, depending upon the cancer antigen we use. We can plug in a specific cancer antigen into this platform, and the vaccine targeted to dendritic cells. The dendritic cells would process and present the right antigen, then generating immune responses (T &B cell) against the cancer. We are also evaluating some bioterrorist viruses, the biological weapons terrorists would use. We just started a project to look at one of those viruses to see if we can come up with the prophylactic vaccines to prevent diseases that would be caused by organism that could be used in bioterrorism.
Interviewer: Would the Chimigen
Dr. Rajan George: It could work for bird flu if we just plugged in the bird flu antigen into the platform. Then we can use it as a prophylactic. It generates antibody to generate B-Cell response. You can produce a prophylactic vaccine using this platform. The Chimigen
Interviewer: How high is your confidence level in producing a prophylactic vaccine for the avian flu virus?
Dr. Rajan George: My thinking is that it is quite high. I think very highly of having a vaccine like that. But, the ultimate proof has to come from humans. Our HepaVaxx B clinical trial will give us a lot of information on how the technology really works. Until then, our optimism is based on laboratory results.
Interviewer: Can you describe what comprises the Chimigen platform?
Dr. Rajan George: The platform has two components. The first one is from the infectious agent. The second component is from a murine monoclonal antibody. Part one is fused with a fragment of part two by recombinant technology to produce a new entity, the Chimigen
Interviewer: How do you produce such a flexible vaccine, one that appears capable of treating nearly any infection?
Dr. Rajan George: To produce a Chimigen
Interviewer: What do you mean when you say, “useful in generating better immune responses”?
Dr. Rajan George: When a person has a chronic virus infection, his or her body ignores the virus and associated proteins. The body treats the virus as part of itself. The body does not recognize this virus as something foreign to it. Therefore the immune system does not attack the virus. But, by combining the virus antigen with a foreign protein such as the murine antibody fragment, the whole chimeric protein now is recognized by the body’s immune system as “foreign,” different from something of its own. In essence, this is a re-education of the immune system to switch its recognition of the virus from “self” to “foreign”.
Interviewer: From where did the scientific model come, and does it have similarities to another ViRexx Medical product, OvaRex MAb®?
Dr. Rajan George: This scientific model arose from discussions among the three lead scientists of the company, Dr. Tony Noujaim, Dr. Lorne Tyrrell, both founders of the company and myself. I am a biochemist by training and the collective thoughts of all of us went into the design of the Chimigen
Interviewer: It sounds as though the Chimigen
Dr. Rajan George: There are similarities and there are differences. OvaRex binds to the antigen CA-125. Then, the CA-125/Ovarex complex binds to the dendritic cells. The complex is internalized and processed. The peptides generated from the antigen are presented to the T cells, and the chain of events in the immune system gets stimulated. The activated cytotoxic T cells eliminate the cancer cells which contain the CA125 antigen. In the case of the Chimigen
Interviewer: How would this work in treating Hepatitis B?
Dr. Rajan George: Developing a treatment for Hepatitis B chronic infection, for someone who already has the infection, would involve re-educating the immune system to react differently than it previously has. The infected person already has this virus and the derived antigens. If you put some more of the same antigens into the person, the person’s immune system is not going to know the difference His body is going to say, “Well, what’s the difference? I already have it. I am not going to do anything with it.” The body will ignore it. That’s what is called tolerance. With the Chimigen
Interviewer: How then have you changed the body’s response to the infection?
Dr. Rajan George: In a Hepatitis B chronic infection, let’s say I have the infection. My system is tolerating the virus. It’s ignoring the presence of the virus. While that is happening, the virus may be causing disease in with my liver. With time, it’s going to get my liver into trouble and my immune system has not responded adequately to remove the threat. We inject the protein – the one we just produced, which we call the Chimigen
Interviewer: And after the vaccine injection, what does the body see?
Dr. Rajan George: The body’s immune system see a new foreign antigen composed of a portion of the mouse monoclonal antibody linked to the viral antigen. It’s a foreign antigen.” The new “chimigen” stimulates an immune response to the antigen as well as the viral antigen. This is very important because the virus antigen was previously being ignored. Now, it’s being recognized as foreign through linked recognition of the mouse antigen as being foreign.
Interviewer: How do the dendritic cells react after they recognize this foreign threat?
Dr. Rajan George: The dendritic cells are the sentries of the immune system. They guard what comes in. When they recognize a “foreign situation,” what does the immune system do? It treats the whole molecule, the whole protein including the virus antigen, as foreign. The dendritic cells chop up this protein into small pieces called peptides. These peptides also are called “epitopes.” There are T cell epitopes which are smaller, and B cell epitopes which are longer. These small peptides bind to MHC I and activate Cytotoxic T lymphocytes (CTLs). The dendritic cells have a system where they put the T-cell epitope on another protein, MHC Class I, and bring it to the surface of the dendritic cell. They are presented as a complex on the surface of the dendritic cell to attract the T-cells. The T-cells come and see this, then get activated. Now, the activation is also specific to the virus protein. There are different varieties of T-cells, but the cytotoxic T-Cells are the most important in eliminating infections that already exist. The activated cytotoxic T-cells are the ones who do the attacking. They are the ones who start killing the virus infected cells.
Interviewer: And what about the B Cells?
Dr. Rajan George: That is the other side to this story. The dendritic cells can present another kind of peptide epitope. There is a second class of peptides, which are also produced when the protein is chopped up. The dendritic cells stimulate the B-Cells, B-Lymphocytes. And B-lymphocytes produce antibodies. The longer peptides bind to MHC II and activate B lymphocytes (B cells). B cells produce antibodies against the peptides. The antibodies are specific to the antigens we put in the Chimigen
Interviewer: Aren’t there a lot of antibodies being investigated as therapeutics?
Dr. Rajan George: There are a lot of antibodies being investigated as therapeutics. OvaRex is the prime example. Avastin and Herceptin are two others, both of which are doing very well in the market. Another is Remicade, which is used to treat diseases such as rheumatoid arthritis. There are antibodies that are in various stages of clinical development, many are humanized antibodies where you want to avoid an immune response to the antibody. Our chimigen technology is new as we are trying to increase the immune response on a virus or a cancer through linked recognition. It is not found anywhere outside of our laboratories. This approach has not been tried before for chronic HBV or HCV infections.
Interviewer: Why would your vaccine work where others have tried and failed?
Dr. Rajan George: The reason is because of the novelty of the technology. We are re-educating the body’s own immune system to do the work by using the Chimigen
Interviewer: Much of the research has been within the laboratory. How much of this is hypothetical?
Dr. Rajan George: Our experiences so far have been mostly with isolated systems, meaning experimental systems outside of the body. For example, ViRexx’s Chimigen