02-28-2013, 04:35 AM
Generally, there are two types of immune response in humans. The first is natural immunity which includes neutrophils, macrophages, NK cells and complement defense system, and the second is acquired immune response which has two branches - cellular and humoral immunity.
Humoral immunity is consisted of B-cells and their products-antibodies, and today’s medicine offers vaccines that stimulate this type of immune response. Cellular immune response includes T-cells which are very important in human immunity, but, until now, no one succeeded to make a vaccine based on this type of immune response. News from this field are described in this article:
Biotechnical company “Genocea” hopes to produce first effective vaccine with T-cells. If true, this could redefine infectious medicine.
Traditional vaccines do not prevent some infectious diseases. Microbes that are hidden inside human cells and that cause chronic diseases are not blocked by the antibodies created as a response to standard vaccines.
Vaccines created by using T-cells, which trigger a different type of immune response, could in theory offer better prevention and control of chronic infection, but so far no one has been successful in the transfer of vaccine T-cells from the laboratory to the clinic.
Officials from biotech company Genocea from Cambridge, Massachusetts, state that high-throughput method, which uses the company, may change all that, says Technologyreview site. Its first clinical project to be tested is an experimental vaccine against herpes.
The Mechanisms of Action
All existing vaccines induce the body to produce antibodies that attach to the surface of microbes that cause infection and mark them for destruction. However, pathogens that live inside cells, such as viruses, some bacteria or other microbes that cause AIDS, malaria, herpes, tuberculosis and chlamydia, can avoid this defense mechanism.
For extracellular microorganisms, humoral immunity represented by B-cells and antibodies is very effective, but not against intracellular microbes. "In order to deal with this type of pathogen, we often had to stimulate what we call cell immunity. Unlike immune antibodies, which recognize pathogens directly, cellular immunity has to recognize your infected cell and to get rid of it," said Darren Higgins, a biologist at Harvard Medical School who is co-founder of Genocea and who studies the interactions between host and pathogen.
The activation of cellular immunity and the family of cells to fight infection as a part of T-cell immune response is a challenge. The method of trial and error, which is used to produce vaccine based on antibodies, does not work with the vaccine with T-cells.
Despite years of academic and industrial labor, and even clinical trials, there is currently no vaccine with T-cells in the market.
"We still do not know all the rules needed to product vaccines with T-cells, nor do we know how much it would be effective," said Robert Brunham, a physician-scientist at University of British Columbia in Vancouver, who is working to develop a T-cell vaccine against the chlamydia.
Indeed, our understanding of how T cells control the infection is still in the developing stage. The real challenge is how to identify the true protein, or antigen of the pathogen that will attract the attention of T-cells so they can signal that human cells contain infectious agents.
"If you can determine which parts the protein contains, then you can use that protein as a vaccine to train your immune system to react exactly as you need to external pathogens," said Higgins, who is now a consultant and scientific advisor in Genocea.
Magnitude of the challenge depends on the number of proteins that are decoded by the genome of pathogens. In thehe herpes simplex 2 each of about 80 proteins can be genome, and over one thousand proteins in Chlamydia and over 5,000 in malaria. Testing of each individual protein is a long and expensive process.
Genocea approach involves collecting as many pathogenic proteins as it reasonably could have been produced in the laboratory, and then observing how the human immune cells react to each of them.
Two Types of Cells Play Important role
Generally, this involves two types of isolation of immune cells in humans - T-cells and antigen-presenting cells, which carry the parts of bacteria or other pathogens on its outer surface and presenting them to T-cells. If T-cells produced immune-signaling molecules in response to a specific antigen, researchers in Genocea believe that specific antigen would be potential candidate for the vaccine.
But there is another level of complication related to the T-cell response, which requires a review of the group of candidates for the vaccine: human genetics.
Protein that triggers a response in one person, may not work for others, because there is a genetic diversity of structures that antigen-presenting cells use to treat antigens.
"In any case, it is a barrier that determines whether we get a universal vaccine or not and this is an area in which we are moving," said Brunhem.
Genocea hopes to approach these problems by testing how T cells respond to immune cells, depending on the genetic basis of diversity.
Genital Herpes Vaccine
Genocea plans to begin clinical trials for the vaccine against genital herpes. If it is successful, Genocea’s vaccines for herpes simplex 2 will be the first to fight against the disease that affects one of every six people aged between 15 and 49. Currently, patients can take antiviral drugs as a therapy, but there is no cure. Candidates for Genocea-vaccine would be the patients who already have the disease.
Genocea program for the vaccine against herpes is growing faster than traditional vaccine research which take sometimes 10 years to cross the path from discovery to the proven concept and as many as 20 years to reach the market, said Higgins.
This achievements are important first step in developing more advanced T-cell vaccines that can be used not only to prevent infectious diseases, but also some autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Crohn's disease and AIDS.
However, sufficient clinical studies have not yet been conducted in order to confirm efficiency, safety and applicability of this new way of treatment.
Humoral immunity is consisted of B-cells and their products-antibodies, and today’s medicine offers vaccines that stimulate this type of immune response. Cellular immune response includes T-cells which are very important in human immunity, but, until now, no one succeeded to make a vaccine based on this type of immune response. News from this field are described in this article:
Biotechnical company “Genocea” hopes to produce first effective vaccine with T-cells. If true, this could redefine infectious medicine.
Traditional vaccines do not prevent some infectious diseases. Microbes that are hidden inside human cells and that cause chronic diseases are not blocked by the antibodies created as a response to standard vaccines.
Vaccines created by using T-cells, which trigger a different type of immune response, could in theory offer better prevention and control of chronic infection, but so far no one has been successful in the transfer of vaccine T-cells from the laboratory to the clinic.
Officials from biotech company Genocea from Cambridge, Massachusetts, state that high-throughput method, which uses the company, may change all that, says Technologyreview site. Its first clinical project to be tested is an experimental vaccine against herpes.
The Mechanisms of Action
All existing vaccines induce the body to produce antibodies that attach to the surface of microbes that cause infection and mark them for destruction. However, pathogens that live inside cells, such as viruses, some bacteria or other microbes that cause AIDS, malaria, herpes, tuberculosis and chlamydia, can avoid this defense mechanism.
For extracellular microorganisms, humoral immunity represented by B-cells and antibodies is very effective, but not against intracellular microbes. "In order to deal with this type of pathogen, we often had to stimulate what we call cell immunity. Unlike immune antibodies, which recognize pathogens directly, cellular immunity has to recognize your infected cell and to get rid of it," said Darren Higgins, a biologist at Harvard Medical School who is co-founder of Genocea and who studies the interactions between host and pathogen.
The activation of cellular immunity and the family of cells to fight infection as a part of T-cell immune response is a challenge. The method of trial and error, which is used to produce vaccine based on antibodies, does not work with the vaccine with T-cells.
Despite years of academic and industrial labor, and even clinical trials, there is currently no vaccine with T-cells in the market.
"We still do not know all the rules needed to product vaccines with T-cells, nor do we know how much it would be effective," said Robert Brunham, a physician-scientist at University of British Columbia in Vancouver, who is working to develop a T-cell vaccine against the chlamydia.
Indeed, our understanding of how T cells control the infection is still in the developing stage. The real challenge is how to identify the true protein, or antigen of the pathogen that will attract the attention of T-cells so they can signal that human cells contain infectious agents.
"If you can determine which parts the protein contains, then you can use that protein as a vaccine to train your immune system to react exactly as you need to external pathogens," said Higgins, who is now a consultant and scientific advisor in Genocea.
Magnitude of the challenge depends on the number of proteins that are decoded by the genome of pathogens. In thehe herpes simplex 2 each of about 80 proteins can be genome, and over one thousand proteins in Chlamydia and over 5,000 in malaria. Testing of each individual protein is a long and expensive process.
Genocea approach involves collecting as many pathogenic proteins as it reasonably could have been produced in the laboratory, and then observing how the human immune cells react to each of them.
Two Types of Cells Play Important role
Generally, this involves two types of isolation of immune cells in humans - T-cells and antigen-presenting cells, which carry the parts of bacteria or other pathogens on its outer surface and presenting them to T-cells. If T-cells produced immune-signaling molecules in response to a specific antigen, researchers in Genocea believe that specific antigen would be potential candidate for the vaccine.
But there is another level of complication related to the T-cell response, which requires a review of the group of candidates for the vaccine: human genetics.
Protein that triggers a response in one person, may not work for others, because there is a genetic diversity of structures that antigen-presenting cells use to treat antigens.
"In any case, it is a barrier that determines whether we get a universal vaccine or not and this is an area in which we are moving," said Brunhem.
Genocea hopes to approach these problems by testing how T cells respond to immune cells, depending on the genetic basis of diversity.
Genital Herpes Vaccine
Genocea plans to begin clinical trials for the vaccine against genital herpes. If it is successful, Genocea’s vaccines for herpes simplex 2 will be the first to fight against the disease that affects one of every six people aged between 15 and 49. Currently, patients can take antiviral drugs as a therapy, but there is no cure. Candidates for Genocea-vaccine would be the patients who already have the disease.
Genocea program for the vaccine against herpes is growing faster than traditional vaccine research which take sometimes 10 years to cross the path from discovery to the proven concept and as many as 20 years to reach the market, said Higgins.
This achievements are important first step in developing more advanced T-cell vaccines that can be used not only to prevent infectious diseases, but also some autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Crohn's disease and AIDS.
However, sufficient clinical studies have not yet been conducted in order to confirm efficiency, safety and applicability of this new way of treatment.