تويت
What are DNA Vaccines?
What are DNA Vaccines
[mouseover=This is a new technique of developing vaccines using the genetics science and an example of the interaction between genetics and immunology...]DNA Vaccines[/mouseover]
Genetic/ DNA immunization is a novel technique used to efficiently stimulate humoral and cellular immune responses to protein antigens. The direct injection of genetic material into a living host causes a small amount of its cells to produce the introduced gene products. This inappropriate gene expression within the host has important immunological consequences, resulting in the specific immune activation of the host against the gene delivered antigen.
Traditional Vaccines: The development of vaccination against harmful pathogenic microorganisms represents an important advancement in the history of modern medicine. In the past, traditional vaccination has relied on two specific types of microbiological preparations to produce material for immunization and generation of a protective immune response. These two categories involve either living infectious material that has been manufactured in a weaker state and therefore inhibits the vaccine from causing disease, or inert, inactivated, or subunit preparations.
Live attenuated vaccines stimulate protective immune responses when they replicate in the host. The viral proteins produced within the host are released into the extracellular space surrounding the infected cells and are then acquired, internalized and digested by scavenger cells that circulate the body. These cells are called antigen presenting cells (APCs) and include macrophages, dendritic cells, and B cells, which work together to expand immune response. The APCs recirculate fragments of the digested the antigen to their surface, attached to MHC class II antigens. This complex of foreign peptide antigen plus host MHC class II antigens forms part of
the specific signal with which APCs along with the MHC peptide complex, trigger the action of of immune cells, the T helper lymphocytes. The second part of the activation signal comes from the APCs themselves, which display on their cell surface constimulatory molecules along with MHC-antigen complexes. Both drive T call expansion and activation through interaction with their respective ligands, the T cell receptor complex (TCR) and the constimulatory receptors CD28/CTLA4, present on the the T cell surface. Activated T cells secrete molecules that act as powerful activates of immune cells. Also as viral proteins are produced within the host cells, small parts of these proteins surface, chaperoned by host cell MHC class I antigens. These complexes together are recognized by a second class of T cells, killer or cytotoxic cells. This recognition, along with other stimulation by APCs and production of cytokine by stimulated T cells, is responsible for the developments of mature cytotoxic T cells (CTL) capable of destroying infected cells. In most instances live infection induces life long immunity. Although live attenuated preparations are the vaccines of choice they do pose the risk of reversion to their pathogenic form, causing infection.
Immune Response
In contrast, when inoculated nonlive vaccines composed of whole or even partial viruses are not produced within the host cells, they mainly end up in the extracellular space. They provide protection by directly generating T helper and humoral immune responses against the pathogenic immunogen. In the absence of the cellular production of the foreign antigen, these vaccines are usually devoid of the ability to induce significant T cytotoxic responses. In addition, these vaccines are not actually produced in the host, and therefore, they are not customized by the host. The immunity induced by their vaccines frequently decreases during the life of the host and may require additional boosters to achieve lifelong immunity. However, nonlive vaccines offer some important advantages over live vaccines: they are produced earlier, and they can be designed to contain only the specific antigenic target of the pathogen that is involved in the development of protective immunity and exclude all other viral components.
Genetic Immunization: Since its early applications in the 1950's, DNA-based immunization has become a novel approach to vaccine
development. Direct injection of naked plasmid DNA induces strong immune responses to the antigen encoded by the gene vaccine. Once the plasmid DNA construct is injected the host cells take up the foreign DNA, expressing the viral gene and producng the corresponding viral protein inside the cell. This form of antigen presentation and processing induced both MHC and class I and class II restricted cellular and humoral immune responses .
History: The use of genetic material to deliver genes for therapeutic purposes has been practiced for many years. Experiments outlining the transfer of DNA into cells of living animals were reported as early as 1950. Later experiments using purified genetic material only further confirmed that the direct DNA gene injection in the absence of viral vectors results in the expression of the inoculated genes in the host. There have been additional experiments that extend these findings to recombinant DNA molecules, further illustrating the idea that purified nucleic acids could be directly delivered into a host and proteins would be produced. In 1992, scientists Tang and Johnson reported that the delivery of human growth hormone in a expression cassette in vivo resulted in production of detectable levels of the growth hormone in host mice. They also found that these inoculated mice developed antibodies against the human growth hormone; they termed this immunization procedure "genetic immunization", which describes the ability of inoculated genes to be individual immunogens .Construction: DNA vaccines are composed of a bacterial plasmids. Expression plasmids used in DNA-based vaccination normally contain two unites: the antigen expression unit composed of promoter/enhancer sequences, followed by antigen-encoding and polyadenylation sequences and the production unit composed of of bacterial sequences necessary for plamid amplification and selection .
The construction of bacterial plasmids with vaccine inserts is accomplished using recombinant DNA technology. Once constructed, the vaccine plasmid is transformed into bacteria, where bacterial growth produces multiple plasmid copies. The plasmid DNA is then purified from the bacteria, by separating the circular plasmid from the much larger bacterial DNA and other bacterial impurities. This purifies DNA acts as the vaccine
.
Limitations: Although DNA can be used to raise immune responses against pathogenic proteins, certain microbes have outer capsids that are made up of polysaccharides. This limits the extent of the usage of DNA vaccines because they cannot substitute for polysaccharide-based subunit vaccines.
Future- It has recently been discovered that the transfection of myocytes can be amplified by pretreatment with local anesthetics or with cardiotoxin, which induce local tissue damage and initiate myoblast regeneration. Gaining a full understanding of this mechanism of DNA uptake could prove helpful in improving applications for gene therapy and gene vaccination. Both improved expression and better engineering of the DNA plasmid may enhance antibody response to the gene products and expand the applications of the gene vaccines .t]
[mouseover=This is a new technique of developing vaccines using the genetics science and an example of the interaction between genetics and immunology...]DNA Vaccines[/mouseover]
Genetic/ DNA immunization is a novel technique used to efficiently stimulate humoral and cellular immune responses to protein antigens. The direct injection of genetic material into a living host causes a small amount of its cells to produce the introduced gene products. This inappropriate gene expression within the host has important immunological consequences, resulting in the specific immune activation of the host against the gene delivered antigen.
Traditional Vaccines: The development of vaccination against harmful pathogenic microorganisms represents an important advancement in the history of modern medicine. In the past, traditional vaccination has relied on two specific types of microbiological preparations to produce material for immunization and generation of a protective immune response. These two categories involve either living infectious material that has been manufactured in a weaker state and therefore inhibits the vaccine from causing disease, or inert, inactivated, or subunit preparations.
Live attenuated vaccines stimulate protective immune responses when they replicate in the host. The viral proteins produced within the host are released into the extracellular space surrounding the infected cells and are then acquired, internalized and digested by scavenger cells that circulate the body. These cells are called antigen presenting cells (APCs) and include macrophages, dendritic cells, and B cells, which work together to expand immune response. The APCs recirculate fragments of the digested the antigen to their surface, attached to MHC class II antigens. This complex of foreign peptide antigen plus host MHC class II antigens forms part of
the specific signal with which APCs along with the MHC peptide complex, trigger the action of of immune cells, the T helper lymphocytes. The second part of the activation signal comes from the APCs themselves, which display on their cell surface constimulatory molecules along with MHC-antigen complexes. Both drive T call expansion and activation through interaction with their respective ligands, the T cell receptor complex (TCR) and the constimulatory receptors CD28/CTLA4, present on the the T cell surface. Activated T cells secrete molecules that act as powerful activates of immune cells. Also as viral proteins are produced within the host cells, small parts of these proteins surface, chaperoned by host cell MHC class I antigens. These complexes together are recognized by a second class of T cells, killer or cytotoxic cells. This recognition, along with other stimulation by APCs and production of cytokine by stimulated T cells, is responsible for the developments of mature cytotoxic T cells (CTL) capable of destroying infected cells. In most instances live infection induces life long immunity. Although live attenuated preparations are the vaccines of choice they do pose the risk of reversion to their pathogenic form, causing infection.
Immune Response
In contrast, when inoculated nonlive vaccines composed of whole or even partial viruses are not produced within the host cells, they mainly end up in the extracellular space. They provide protection by directly generating T helper and humoral immune responses against the pathogenic immunogen. In the absence of the cellular production of the foreign antigen, these vaccines are usually devoid of the ability to induce significant T cytotoxic responses. In addition, these vaccines are not actually produced in the host, and therefore, they are not customized by the host. The immunity induced by their vaccines frequently decreases during the life of the host and may require additional boosters to achieve lifelong immunity. However, nonlive vaccines offer some important advantages over live vaccines: they are produced earlier, and they can be designed to contain only the specific antigenic target of the pathogen that is involved in the development of protective immunity and exclude all other viral components.
Genetic Immunization: Since its early applications in the 1950's, DNA-based immunization has become a novel approach to vaccine
development. Direct injection of naked plasmid DNA induces strong immune responses to the antigen encoded by the gene vaccine. Once the plasmid DNA construct is injected the host cells take up the foreign DNA, expressing the viral gene and producng the corresponding viral protein inside the cell. This form of antigen presentation and processing induced both MHC and class I and class II restricted cellular and humoral immune responses .
History: The use of genetic material to deliver genes for therapeutic purposes has been practiced for many years. Experiments outlining the transfer of DNA into cells of living animals were reported as early as 1950. Later experiments using purified genetic material only further confirmed that the direct DNA gene injection in the absence of viral vectors results in the expression of the inoculated genes in the host. There have been additional experiments that extend these findings to recombinant DNA molecules, further illustrating the idea that purified nucleic acids could be directly delivered into a host and proteins would be produced. In 1992, scientists Tang and Johnson reported that the delivery of human growth hormone in a expression cassette in vivo resulted in production of detectable levels of the growth hormone in host mice. They also found that these inoculated mice developed antibodies against the human growth hormone; they termed this immunization procedure "genetic immunization", which describes the ability of inoculated genes to be individual immunogens .Construction: DNA vaccines are composed of a bacterial plasmids. Expression plasmids used in DNA-based vaccination normally contain two unites: the antigen expression unit composed of promoter/enhancer sequences, followed by antigen-encoding and polyadenylation sequences and the production unit composed of of bacterial sequences necessary for plamid amplification and selection .
The construction of bacterial plasmids with vaccine inserts is accomplished using recombinant DNA technology. Once constructed, the vaccine plasmid is transformed into bacteria, where bacterial growth produces multiple plasmid copies. The plasmid DNA is then purified from the bacteria, by separating the circular plasmid from the much larger bacterial DNA and other bacterial impurities. This purifies DNA acts as the vaccine
.
Limitations: Although DNA can be used to raise immune responses against pathogenic proteins, certain microbes have outer capsids that are made up of polysaccharides. This limits the extent of the usage of DNA vaccines because they cannot substitute for polysaccharide-based subunit vaccines.
Future- It has recently been discovered that the transfection of myocytes can be amplified by pretreatment with local anesthetics or with cardiotoxin, which induce local tissue damage and initiate myoblast regeneration. Gaining a full understanding of this mechanism of DNA uptake could prove helpful in improving applications for gene therapy and gene vaccination. Both improved expression and better engineering of the DNA plasmid may enhance antibody response to the gene products and expand the applications of the gene vaccines .t]
تعليق