Prof RN Basu 181 • What is Vaccine? o A biological preparation that elicits immunity to a particular disease. o In addition to the antigen, it can contain multiple components, such as adjuvants, preservatives, stabilizers, each of which may have specific safety implications. 26 • Immunity27 o 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 182 • Active Immunity o Active immunity is protection that is produced by the person’s own immune system o This type of immunity usually lasts for many years, often during a lifetime • Passive immunity o It is protection by products produced by an animal or human and transferred to another human, usually by injection o Passive immunity often provides effective protection, but this protection wanes (disappears) with time, usually within a few weeks or months 183 o The immune system is a complex system of interacting cells The primary purpose is to identify foreign (“nonself”) substances These foreign substances are known as antigens o Antigens can be: Live: . such as viruses and bacteria Inactivated: o The immune system develops a defense against the antigen The defense is known as the immune response 184 This involves production of proteins molecules by B lymphocytes . These protein molecules are called antibodies (or immunoglobulin) Also specific cells are produced . These cells include T-lymphocytes The cell production is known as cell-mediated immunity The purpose of these specialised cells is elimination of foreign substances o The most effective immune responses are produced by a live antigen The antigen need not always be alive as occurs with natural infection with a virus or bacterium, to produce an immune response 185 o Some proteins, such as hepatitis B surface antigen are easily recognised by the immune system o Other material, such as polysaccharide, are less effective antigens Polysaccharides are the constituent material of cell wall of some bacteria o Polysaccharides may not produce as good response as in protein antigens • Passive Immunity o Immunity produced by another human or animal is transferred to another man or animal 186 o Passive immunity is temporary and provides protection only for sometime against some infections Antibodies will degrade during a period of weeks to month and will no longer be available for protection o Most common form of immunity is what an infant receives from its mother Mother’s immunity is transferred to the foetus through placenta during the last one or two months of pregnancy o A full term infant will have the same immunity as that of its mother and that will protect the infant for up to one year 187 • Sources of passive immunity o Many blood products contain antibody Specific Immune gamma globulin which is contained in plasma provides protection against that specific infection . Washed or reconstituted red blood cells contain very little antibody Some other plasma products such as intravenous immune globulin contain large amount of antibody o In addition, there are three other major sources of antibody used for therapeutic purposes 188 o These are: 1. Homologous pooled human antibody 2. Homologous human hyperimmune globulin, and 3. Homologous hyperimmune serum o Homologous pooled human antibody is also known as immune globulin It is produced by combining (pooling) the Immunoglobulin G (IgG) antibody from serum of many thousand adult donors . As it is pooled, it contains antibody from many different antigens It is mainly used for postexposure prophylaxis for hepatitis A and measles and treatment of certain congenital immunoglobulin deficiencies 189 o Homologous (from same evolutionary origin) human hyperimmune globulin contains high titres (concentration) of specific antibody This also contains other antibodies of lesser concentration The hyperimmune globulins are used for postexposure prophylaxis for several diseases: . Such as, hepatitis B, rabies, tetanus, and varicella o Heterologous (from animals, usually horses) hyperimmune serum is also known as antitoxin These serum contains antibody against only one antigen 190 o Monoclonal antibody Immune globulin from human sources is polyclonal . It contains different kinds of antibodies Techniques are available to produce antibody from single clone of B cells . Monoclonal is one that appears to be a copy of an original form Monoclonal antibody acts against only one kind of antigen or only a group of related antigen Certain antibody products like immune globulin may interfere with live virus vaccines Monoclonal antibodies have many uses . This includes, diagnosis of certain form of cancer, treatment of cancer, prevention of transplant rejection and treatment of autoimmune diseases 191 • Active Immunity o Body’s immune system is stimulated to produce specific humoral antibody and cellular antibody Active immunity lasts for a long time for years or even for lifetime o Natural infection with an organism produces active immunity The duration of protection may be lifelong . Exception: malaria o The persistence of protection after the infection for several years is known as immunologic memory 192 After the exposure of immune system B memory cells are produced . These B cells continue to circulate in blood and also reside in the bone marrow for many years . When another exposure to the antigen occurs, these memory cells begin to replicate and produce antibody quickly to protect the organism Active immunity is also produced by vaccination . Vaccination produce immunity in the same way as natural infection . However, the individual does not suffer from the disease or the disease related complications . Many vaccines also produce immunologic memory like natural disease 193 • Principles of Vaccination o There are many factors that affects immunity development following vaccination o These are: Presence of maternal antibody Nature and dose of antigen Route of administration Presence of an adjuvant Host factors: . Age, nutritional factors, genetics, and coexisting diseases 194 • Classification of vaccines o Two basic types: 1. Live attenuated 2. Inactivated o The characteristics of these two types are different These characteristics determine how the vaccine is used o Live attenuated vaccines are produced by modifying the “wild” virus or bacterium in a laboratory “Wild “means disease producing 195 o The altered organism retains the ability to multiply and produce immunity This altered organism do not produce any disease o Inactivated vaccines can be made up of either the whole virus or bacterium, or fractions of any of these Fractional vaccines are either protein based or polysaccharide based Protein based vaccines include toxoids and subunit or subviron products Polysaccharide vaccines are mostly composed of pure cell wall polysaccharide from bacteria Conjugate polysaccharide vaccines contain chemically linked to a protein . This protein bonding makes the conjugate vaccine more potent 196 o General rule of a vaccine The more similar a vaccine is to the disease producing form of the organism, the better the immune response to the vaccine • Live Attenuated Vaccines o These vaccines are made from “wild” or disease-causing viruses or bacteria These viruses or bacteria are attenuated or weakened in a laboratory usually by repeated culturing Example: . Measles virus was isolated from a child in 1954 . It took 10 years of serial passage in tissue culture media to transform into attenuated vaccine virus 197 o Immune response from a live attenuated virus requires that the virus must multiply in the recipient of vaccine o A small dose of live attenuated vaccine is administered It replicates into enough number of organism to be able to produce immunity If the live organism in the vaccine is damaged somehow like by heat or sunlight, or . Anything that interferes with replication of the organism in the body, the vaccine becomes ineffective 198 o Live attenuated vaccine do not produce disease as the ‘wild’ organism does Even if it does, the disease is much milder than the natural disease . In this case, it is described as adverse reaction o The immune response from live attenuated vaccine is almost similar to natural infection by the wild form of the organism The immune system does not differentiate between an infection with a weakened vaccine virus and an infection with a wild virus Parenteral administration of live attenuated vaccine usually requires only a single dose to produce immunity in most recipients 199 o A small percentage of recipients may need two doses to produce immunity o Live attenuated virus may cause severe or fatal reactions This is because of uncontrolled replication of the vaccine virus . This occurs in recipients who are immunodefficient, or being treated with certain drugs or are with HIV infection . Theoretically, a live attenuated virus may revert to its original pathogenic form . This is known to happen with live oral polio vaccine 200 o Active immunity from a live attenuated vaccine may not develop due to circulating antibody to the vaccine virus The circulating antibody may come from many sources such as transplacental maternal antibody, or transfusion The poor response from vaccination is referred to as vaccine failure o Live attenuated vaccines are delicate and should be handled and stored with care o Currently available live attenuated vaccines: The viral vaccines are: Measles, mumps, rubella, vaccinia, varicella, zoster, yellow