- 26 Kasım 2012
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How do RNA-based vaccines work?
Vaccination is the process in which substances called antigens are introduced artificially into the body to stimulate the immune system, the set of cells that protects the body against infections [2,3]. Those antigens are generally infectious agents – pathogens – that have been inactivated by heat or chemical treatment so that they will not cause disease, or they can also be purified proteins from the pathogens. Exposing the body to antigens leads to the production of molecules specifically directed against them, called antibodies. Antibodies create a memory of a specific pathogen (“acquired immunity”) and enable a more rapid and efficient response to a real infection with an active pathogen.
Vaccination has been central in diminishing or eradicating multiple infectious diseases, such as smallpox or polio. However, producing vaccines is a long and complex process, and it has been difficult to implement vaccines against certain pathogens. Thus, designing new vaccines remains a major challenge for public health. To answer this challenge, there have been many improvements to designing vaccines, such as using computational prediction. Development of nucleotide vaccines based on DNA, and the related molecule RNA, is another promising area of progress in the field [4].
In each cell of a living organism, DNA is the molecule that contains the genetic information of the organism [5]. It is composed of a series of four building blocks, whose sequence gives the instructions to fabricate proteins. This process requires a transient intermediary called messenger RNA that carries the genetic information to the cell machinery responsible for protein synthesis. As an analogy, one can see the DNA as a cook book in a library: the recipe is stored here but cannot be used. The commis, or chef’s assistant, first makes a copy (the RNA) of a specific recipe and brings it to the kitchen. The information is now ready-to-use by the chef, who can add the ingredients in the order specified by the recipe and create a cake (the protein).
Figure 1: RNA vaccine technology. An RNA is injected in the body (left). This RNA encodes the information to produce the antigen, which is a protein from a pathogen, that will stimulate the immune system. Inside the cells, the RNA is used to synthesize the antigen, which is exposed to the cell surface (middle). Then, a subset of immune system cells recognizes the antigen and trigger an immune response (direct response and long-term memory) (right).
For a classical vaccine, the antigen is introduced in the body to produce an immune response. However, in the case of DNA- or RNA-based vaccines, no antigen is introduced, only the RNA or DNA containing the genetic information to produce the antigen. That is, for this specific class of vaccines, introduction of DNA and RNA provides the instructions to the body to produce the antigen itself (Figure 1). They can be injected in various ways (under the skin, in the vein or in lymph nodes) and then they can enter our body’s cells. Those cells will use the RNA sequence of the antigen to synthesize the protein [2,6]. After this step, the mechanism is similar to classical vaccines: the antigen is presented at the surface of a subset of cells and triggers the activation of specific cells of the immune system (Figure 2).
The ways in which DNA and RNA vaccines work are similar in many ways, and some of the common steps are described above. However, RNA vaccines have some distinct advantages. One is that RNA-based vaccines appear to perform better than DNA-based vaccines. Another is that they are also safer, as injection of RNA presents no risk of disrupting the cell’s natural DNA sequence. To continue our kitchen analogy, disruption from DNA is like inserting a foreign ingredient in an existing recipe, which can change the resulting dish [2]. Injecting RNA, on the other hand, is like temporarily adding a new recipe in the cook book while keeping old ones untouched, and therefore will not result in surprising changes to existing recipes.
Figure 2: Disease prevention. Vaccination with RNA induces a primary response (top) by instructing the body’s cells to produce an antigen that is presented to the immune system. This activates specific cells, which create a memory for this antigen. Later, when the real pathogen is present (bottom), those cells recognize the same antigen and react rapidly and strongly against the infectious agent (secondary response).
Vaccination is the process in which substances called antigens are introduced artificially into the body to stimulate the immune system, the set of cells that protects the body against infections [2,3]. Those antigens are generally infectious agents – pathogens – that have been inactivated by heat or chemical treatment so that they will not cause disease, or they can also be purified proteins from the pathogens. Exposing the body to antigens leads to the production of molecules specifically directed against them, called antibodies. Antibodies create a memory of a specific pathogen (“acquired immunity”) and enable a more rapid and efficient response to a real infection with an active pathogen.
Vaccination has been central in diminishing or eradicating multiple infectious diseases, such as smallpox or polio. However, producing vaccines is a long and complex process, and it has been difficult to implement vaccines against certain pathogens. Thus, designing new vaccines remains a major challenge for public health. To answer this challenge, there have been many improvements to designing vaccines, such as using computational prediction. Development of nucleotide vaccines based on DNA, and the related molecule RNA, is another promising area of progress in the field [4].
In each cell of a living organism, DNA is the molecule that contains the genetic information of the organism [5]. It is composed of a series of four building blocks, whose sequence gives the instructions to fabricate proteins. This process requires a transient intermediary called messenger RNA that carries the genetic information to the cell machinery responsible for protein synthesis. As an analogy, one can see the DNA as a cook book in a library: the recipe is stored here but cannot be used. The commis, or chef’s assistant, first makes a copy (the RNA) of a specific recipe and brings it to the kitchen. The information is now ready-to-use by the chef, who can add the ingredients in the order specified by the recipe and create a cake (the protein).
Figure 1: RNA vaccine technology. An RNA is injected in the body (left). This RNA encodes the information to produce the antigen, which is a protein from a pathogen, that will stimulate the immune system. Inside the cells, the RNA is used to synthesize the antigen, which is exposed to the cell surface (middle). Then, a subset of immune system cells recognizes the antigen and trigger an immune response (direct response and long-term memory) (right).
For a classical vaccine, the antigen is introduced in the body to produce an immune response. However, in the case of DNA- or RNA-based vaccines, no antigen is introduced, only the RNA or DNA containing the genetic information to produce the antigen. That is, for this specific class of vaccines, introduction of DNA and RNA provides the instructions to the body to produce the antigen itself (Figure 1). They can be injected in various ways (under the skin, in the vein or in lymph nodes) and then they can enter our body’s cells. Those cells will use the RNA sequence of the antigen to synthesize the protein [2,6]. After this step, the mechanism is similar to classical vaccines: the antigen is presented at the surface of a subset of cells and triggers the activation of specific cells of the immune system (Figure 2).
The ways in which DNA and RNA vaccines work are similar in many ways, and some of the common steps are described above. However, RNA vaccines have some distinct advantages. One is that RNA-based vaccines appear to perform better than DNA-based vaccines. Another is that they are also safer, as injection of RNA presents no risk of disrupting the cell’s natural DNA sequence. To continue our kitchen analogy, disruption from DNA is like inserting a foreign ingredient in an existing recipe, which can change the resulting dish [2]. Injecting RNA, on the other hand, is like temporarily adding a new recipe in the cook book while keeping old ones untouched, and therefore will not result in surprising changes to existing recipes.
Figure 2: Disease prevention. Vaccination with RNA induces a primary response (top) by instructing the body’s cells to produce an antigen that is presented to the immune system. This activates specific cells, which create a memory for this antigen. Later, when the real pathogen is present (bottom), those cells recognize the same antigen and react rapidly and strongly against the infectious agent (secondary response).
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