Principles of Vaccination Principles of Vaccination Immunology and Vaccine-Preventable Diseases mmu ,and a detailed d th g of the hasic e scope c f thi text.However,an eful in he basis of recommendations for their use.The description that follows is simplified.Many cellent imr unology textbooks are available to provide additional detail. Immunity is the ability of the human body to tolerate the presence of material indigenous to the body ("self"),and to Principles of Vaccination ability provides protection from infectious disease,since onf rom infectious disease,since Protection from infectious disease foreign by the immun system.Immunity to a microbe is us lly indicated by the ceby thepres presence that orga ism Immunity is generally Very specific to a single organism anisms for Active immunity is protection that is produced by the person's own immune system.This type of immunity is Principles of Vaccination usually permanent. Passive immunity is protection by products produced by an animal or human and transferred to another human,usually by injection.Passive immunity often provides effective protection,but thi s protection wanes(disappears)with time, protection that wanes usually within a few weeks or months The immune system is a com plex system of in Principles of Vaccination prima eign live (such as s and bagen either ted The immune s tem develops a defense against the antig This defense is known as the immune re involves the production of protein molecules,called antibodies (or immunoglobulins),and of specific cells (also n)producedby known as cell-mediated immunity)whose purpose is to facilitate the elimination of foreign substances. toliv ign Howeverantigen produced in response to a live antigen not ne infection ith to be a mun respon chas hepati ace antiger such as charide (o make up the ell wall of certain bacteria)are less effective antigens,and the immune response may not provide as good protection. 1
1 Principles of Vaccination Immunology and Vaccine-Preventable Diseases Immunology is a complicated subject, and a detailed discussion of it is beyond the scope of this text. However, an understanding of the basic function of the immune system is useful in order to understand both how vaccines work and the basis of recommendations for their use. The description that follows is simplified. Many excellent immunology textbooks are available to provide additional detail. Immunity is the ability of the human body to tolerate the presence of material indigenous to the body (“self”), and to eliminate foreign (“nonself”) material. This discriminatory ability provides protection from infectious disease, since most microbes are identified as foreign by the immune system. Immunity to a microbe is usually indicated by the presence of antibody to that organism. Immunity is generally very specific to a single organism or group of closely related organisms. There are two basic mechanisms for acquiring immunity, active and passive. Active immunity is protection that is produced by the person’s own immune system. This type of immunity is usually permanent. Passive immunity is protection by products produced by an animal or human and transferred to another human, usually by injection. Passive immunity often provides effective protection, but this protection wanes (disappears) with time, usually within a few weeks or months. The immune system is a complex system of interacting cells whose primary purpose is to identify foreign (“nonself”) substances referred to as antigens. Antigens can be either live (such as viruses and bacteria) or inactivated. The immune system develops a defense against the antigen. This defense is known as the immune response and usually involves the production of protein molecules, called antibodies (or immunoglobulins), and of specific cells (also known as cell-mediated immunity) whose purpose is to facilitate the elimination of foreign substances. The most effective immune responses are generally produced in response to a live antigen. However, an antigen does not necessarily have to be alive, as occurs with infection with a virus or bacterium, to produce an immune response. Some proteins, such as hepatitis B surface antigen, are easily recognized by the immune system. Other material, such as polysaccharide (long chains of sugar molecules that make up the cell wall of certain bacteria) are less effective antigens, and the immune response may not provide as good protection. Principles of Vaccination 1
Principles of Vaccination Passive Immunity Passive Immunity Passive immunity is the transfer of antibody produced by one human or other animal to another.Pass sive immunity temporary. .Temporary protection longer be prorected nonths, cpieatwalnd Asa result.a full-rerm will have the as its mother.These antibodies will protect the infant from some di Virtually all types of blood products contain antibody.Some Sources of Passive Immunity products (e.g.,washed or reconstituted red blood cells) ·Almos all blood or blood Heme99ctspooledbgma contain Hoemeioaousehgognin In addition to blood products used for transfusion (e.g. whole blood,red cells,and platelets)there are three major sources of antibody used in human medicine.The are yper Homologous pooled human antibody is also known as donors in tib comes fro used postexposure prophyxs for hepatitisA and measles. ne globulins ar high levels of the antibody of interest.However,since other ar eases Heterologous hyperimmune serum is also known as horses labley one and dipbr with this product is serum sickness,a reaction to the horse protein
1 Passive Immunity Passive immunity is the transfer of antibody produced by one human or other animal to another. Passive immunity provides protection against some infections, but this protection is temporary. The antibodies will degrade during a period of weeks to months, and the recipient will no longer be protected. The most common form of passive immunity is that which an infant receives from its mother. Antibodies are transported across the placenta during the last 1–2 months of pregnancy. As a result, a full-term infant will have the same antibodies as its mother. These antibodies will protect the infant from certain diseases for up to a year. Protection is better against some diseases (e.g., measles, rubella, tetanus) than others (e.g., polio, pertussis). Virtually all types of blood products contain antibody. Some products (e.g., washed or reconstituted red blood cells) contain a relatively small amount of antibody, and some (e.g., intravenous immune globulin and plasma products) contain a large amount. In addition to blood products used for transfusion (e.g., whole blood, red cells, and platelets) there are three major sources of antibody used in human medicine. These are homologous pooled human antibody, homologous human hyperimmune globulin, and heterologous hyperimmune serum. Homologous pooled human antibody is also known as immune globulin. It is produced by combining (pooling) the IgG antibody fraction from thousands of adult donors in the United States. Because it comes from many different donors, it contains antibody to many different antigens. It is used primarily for postexposure prophylaxis for hepatitis A and measles. Homologous human hyperimmune globulins are antibody products that contain high titers of specific antibody. These products are made from the donated plasma of humans with high levels of the antibody of interest. However, since hyperimmune globulins are from humans, they also contain other antibodies in lesser quantities. Hyperimmune globulins are used for postexposure prophylaxis for several diseases, including hepatitis B, rabies, tetanus, and varicella. Heterologous hyperimmune serum is also known as antitoxin. This product is produced in animals, usually horses (equine), and contains antibodies against only one antigen. In the United States, antitoxin is available for treatment of botulism and diphtheria. A problem with this product is serum sickness, a reaction to the horse protein. Principles of Vaccination 2
Principles of Vaccination Immune globulin from huma Monoclonal Antibody techniques were developed to isolate and"immortalize" 8oa nonoc an y is 气。 no cloely related group of antigens.Monoclonal 2d antibody products have many applications,including the diagnosis of certain types of cancer(colorectal,prostate, lymphoma t of (Crohn disease,rheumatoid arthritis) and infectious diseases Two globulin products are available for vention or Antibody for Prevention of RSV hyperimmune globulin from buman donors.It contains .RSV-IGIV -hum antibody other than RSV,like other hyperimmune globulin products.Palivizumab is a humanized monoclonal antibody not cnotherb .Palivizumab(Synagis) -monoclonal ontains only RSV antibody Active Immunity Active immunity is sti mlntgmpef Vaccination unity sually lasts s for lifetime. from infectiou nit the infection is known as immunolouic memory.Following exposure of the immune system to an antigen,certain cells tablish e immu and its potential complications.Vaccines produce enmaersnbrotaanqad65iariae
1 Immune globulin from human sources is polyclonal; it contains many different kinds of antibodies. In the 1970s, techniques were developed to isolate and “immortalize” (cause to grow indefinitely) single B cells, which led to the development of monoclonal antibody products. Monoclonal antibody is produced from a single clone of B cell, so these products contain antibody to only one antigen or closely related group of antigens. Monoclonal antibody products have many applications, including the diagnosis of certain types of cancer (colorectal, prostate, ovarian, breast), treatment of cancer (B-cell chronic lymphocytic leukemia, non-Hodgkin lymphoma), prevention of transplant rejection, and treatment of autoimmune diseases (Crohn disease, rheumatoid arthritis) and infectious diseases. Two globulin products are available for the prevention or treatment of respiratory syncytial virus (RSV) infection: RSV-IGIV and palivizumab (Synagis). RSV-IGIV is a hyperimmune globulin from human donors. It contains antibody other than RSV, like other hyperimmune globulin products. Palivizumab is a humanized monoclonal antibody specific for RSV. It does not contain any other antibody except RSV antibody. Active Immunity Active immunity is stimulation of the immune system to produce antigen-specific humoral (antibody) and cellular immunity. Unlike passive immunity, which is temporary, active immunity usually lasts for many years, often for a lifetime. One way to acquire active immunity is to have the natural disease. In general, once persons recover from infectious diseases, they will have lifelong immunity to that disease. The persistence of protection for many years after the infection is known as immunologic memory. Following exposure of the immune system to an antigen, certain cells (memory B cells) continue to circulate in the blood (and also reside in the bone marrow) for many years. Upon reexposure to the antigen, these memory cells begin to replicate and produce antibody very rapidly to reestablish protection. Another way to produce active immunity is by vaccination. Vaccines interact with the immune system and often produce an immune response similar to that produced by the natural infection, but they do not subject the recipient to the disease and its potential complications. Vaccines produce immunologic memory similar to that acquired by having the natural disease. Principles of Vaccination 3
Principles of Vaccination Many factors may influence the immune response to vaccination.These include the presence of maternal antibody nature and dose of antigen,route of administration,and the niamagentics,and Classification of Vaccines There are two basic types of vaccines:live attenuated and Classification of Vaccines cterial Inactivated Live attenuated vaccines are produced by modifving a disease-producing ("wild")virus or bacterium in a laboratory. The resulting vaccine organism retains the ability to replicate (grow）an nd produce imm nity,but ust ly does not in the United Sy live vin ses Ho Inactivated Vaccines heatemaiedaiealvacingaC,Hombbo Inactivated vaccines can be compos d of either whole or bacteria.o e,actioplacines bsed vaccines include tooids (inactivated bacteral oxin) and subunit or subvirion products.Most polysaccharide-based vaccines are composed of pure cell wall polysaccharide from po are those in This inke General Rule The more similar a vaccine is to the disease causing form of the organism,the better the immune response to the vaccine. Live Attenuated Vaccines Live Attenuated Vaccines tenateemeakpelsoamot iruses or b are Must replicate to be effective la ratory,us ally h y repea ‘mar to isolated from a child with measles disease in 1954.Almost Usually effective with one dose 10 years of serial passage using tissue culture media was required to transform the wild virus into vaccine virus
1 Many factors may influence the immune response to vaccination. These include the presence of maternal antibody, nature and dose of antigen, route of administration, and the presence of adjuvants (e.g., aluminum-containing materials added to improve the immunogenicity of the vaccine). Host factors such as age, nutritional factors, genetics, and coexisting disease, may also affect the response. Classification of Vaccines There are two basic types of vaccines: live attenuated and inactivated. The characteristics of live and inactivated vaccines are different, and these characteristics determine how the vaccine is used. Live attenuated vaccines are produced by modifying a disease-producing (“wild”) virus or bacterium in a laboratory. The resulting vaccine organism retains the ability to replicate (grow) and produce immunity, but usually does not cause illness. The majority of live attenuated vaccines available in the United States contain live viruses. However, two live attenuated bacterial vaccines are also available. Inactivated vaccines can be composed of either whole viruses or bacteria, or fractions of either. Fractional vaccines are either protein-based or polysaccharide-based. Proteinbased vaccines include toxoids (inactivated bacterial toxin) and subunit or subvirion products. Most polysaccharide-based vaccines are composed of pure cell wall polysaccharide from bacteria. Conjugate polysaccharide vaccines are those in which the polysaccharide is chemically linked to a protein. This linkage makes the polysaccharide a more potent vaccine. Live Attenuated Vaccines Live vaccines are derived from “wild,” or disease-causing, viruses or bacteria. These wild viruses or bacteria are attenuated, or weakened, in a laboratory, usually by repeated culturing. For example, the measles vaccine used today was isolated from a child with measles disease in 1954. Almost 10 years of serial passage using tissue culture media was required to transform the wild virus into vaccine virus. Principles of Vaccination 4 The more similar a vaccine is to the diseasecausing form of the organism, the better the immune response to the vaccine. General Rule
Principles of Vaccination To produce an imm to stimul vial or interferes with replication of the or nism in the bodt (circulating antibody)can cause the vaccine to be ineffective. ism.Whe a live a ated yac "disease,"it is usually much milder than the natural disease and is referred to as an adverse reaction. a na The immune system does not differentiate between an infection with a weakened vaccine virus and an infection e attenuate ose,except those a ally Live attenuated vaccines may cause severe or fatal reactions as a result of uncontrolled replication (growth)of the vaccine persons ith immunodeficiency A live attenuated vaccine virus could theoretically revert e )ne Active immunity from a live attenuated vaccine may not develop because of interference from circulating antibody Live Attenuated Vaccines to the .Severe reactions possible can in failure） Measles vaccine virus seems to be most sensitive to f2emeyordand deove hea d ighhey mut b all胃edd live attenua n he da stored carefully. Live Attenuated Vaccines and influenza (intranasal).Oral polio vaccine is a live viral Viral oodpeg Bacterial
1 To produce an immune response, live attenuated vaccines must replicate (grow) in the vaccinated person. A relatively small dose of virus or bacteria is administered, which replicates in the body and creates enough of the organism to stimulate an immune response. Anything that either damages the live organism in the vial (e.g., heat, light) or interferes with replication of the organism in the body (circulating antibody) can cause the vaccine to be ineffective. Although live attenuated vaccines replicate, they usually do not cause disease such as may occur with the “wild” form of the organism. When a live attenuated vaccine does cause “disease,” it is usually much milder than the natural disease and is referred to as an adverse reaction. The immune response to a live attenuated vaccine is virtually identical to that produced by a natural infection. The immune system does not differentiate between an infection with a weakened vaccine virus and an infection with a wild virus. Live attenuated vaccines are usually effective with one dose, except those administered orally. Live attenuated vaccines may cause severe or fatal reactions as a result of uncontrolled replication (growth) of the vaccine virus. This only occurs in persons with immunodeficiency (e.g., from leukemia, treatment with certain drugs, or human immunodeficiency virus (HIV) infection). A live attenuated vaccine virus could theoretically revert to its original pathogenic (disease-causing) form. This is known to happen only with live (oral) polio vaccine. Active immunity from a live attenuated vaccine may not develop because of interference from circulating antibody to the vaccine virus. Antibody from any source (e.g., transplacental, transfusion) can interfere with growth of the vaccine organism and lead to poor response or no response to the vaccine (also known as vaccine failure). Measles vaccine virus seems to be most sensitive to circulating antibody. Polio and rotavirus vaccine viruses are least affected. Live attenuated vaccines are fragile and can be damaged or destroyed by heat and light. They must be handled and stored carefully. Currently available live attenuated viral vaccines are measles, mumps, rubella, vaccinia, varicella, yellow fever, and influenza (intranasal). Oral polio vaccine is a live viral vaccine but is no longer available in the United States. A new live recombinant rotavirus vaccine may be licensed in the future. Live attenuated bacterial vaccines are bacille Calmette-Guérin (BCG) and oral typhoid vaccine. Principles of Vaccination 5