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More About Vaccines

We believe that a common problem with past attempts to develop cancer and modern viral vaccines has been due to efforts which mistakenly try to elicit an anti-cancer or anti-viral immune response in the same manner and of the same type as was successful in childhood vaccines development. Childhood vaccines are effective in protecting against a variety of diseases, such as chicken pox (varicella), diphtheria, measles, mumps, tetanus and pertussis. These vaccines are given to healthy children to prevent disease. They incorporate antigen(s) from the disease organisms that are designed to elicit an antibody immune response that neutralizes the pathogens before they develop into disease.  However, while antibodies are effective in neutralizing pathogens found outside of cells, viruses generally are resident and replicate inside of cells where they cannot be recognized by antibodies.

Some viruses like hepatitis B can be neutralized by antibodies if present prior to infection to prevent them from entering cells, however once the disease is established the vaccine is unable to provide a therapeutic effect through eliciting an antibody response.  Some viruses like HIV and SARS-CoV-2 (the virus that causes COVID-19) are capable of infecting cells through cell-to-cell contact (syncytia). This feature provides a mechanism for these viruses to evade neutralizing antibody activity.

The immune system can respond to vaccines with either a humoral (antibody) response or a cellular response (or mixture).  Cellular immunity is generally considered the most desired immune response against cancers and viruses.  However, as the antibody and cellular responses can cancel each other, a strong humoral response can sometimes make you more susceptible to disease, rather than protect you from disease.  It is much more technically difficult to elicit a pure cellular immune response to an antigen than it is to elicit an antibody response.  Therefore, development of vaccines designed to elicit cellular immune responses have not been successfully translated into clinical applications.

The first decision when designing a vaccine is to determine the antigen to be used for immune education. For decades researchers have unsuccessfully attempted to identify antigens on the surface of tumors or viral infected cells that distinguish the abnormal cells from normal cells. However, tumors and viral infected cells do not display unique antigens on their surface that can be recognized by immune cells.  Immune cells recognize antigens displayed within molecules known as MHC molecules.   Killer T-cells (or CTL) recognize antigens in association with MHC class I molecules. To date, no tumor-specific surface molecules have been identified.

There are only surface molecules which are expressed at higher density on tumors or viral infected cells.  These surface markers can be recognized by antibodies, but not killer cells.  Antibodies are ineffective in eliminating cancer or viral infected cells with over-expressed surface markers.  Further, even if antigens are identified that can be recognized by CTL on MHC I molecules, a major complication is that tumors and viral infected cells generally down-regulate MHC I molecule expression to hide from killer cells.

A persistent technical problem is to determine what antigen a cancer or viral vaccine should target. Cancers are caused by a multitude of gene mutations, so developing a vaccine to target all possible mutations is likely impossible.   Viral infected cells can display a wide abundance of peptide antigens which can vary cell by cell and person to person.  Different tumor cells or viral infected cells in the same person display a heterogenous array of peptide antigens. So, every cell could conceivably display a different antigen.  Therefore, a wide array of antigens targets may be needed in order to elicit a protective or therapeutic immune response.   This creates a difficult technological obstacle to developing vaccines with a dominant cellular immune response.

The advantage of Mirror Effect® technology is that through harnessing the power of in-situ vaccination mechanisms, customized cellular immune responses can be elicited in individuals without the need for knowledge of the array of antigens the immune system will recognize.

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