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Lec 10 Virology A Vaccine is a biological preparation that enhances immunity to a particular disease. *Introduction A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to produce specific antibodies or a cellular immune response that destroys or neutralizes the microorganism or its toxins. Immunization against hepatitis A and B, diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), polio, rotavirus, measles, mumps, rubella, varicella-zoster virus (VZV), pneumococcus, influenza, meningococcus, and human papillomavirus. *Types of vaccines : Vaccines are 1- live, attenuated microorganisms: When live pathogens are used, they are attenuated (weakened) to preclude clinical consequences of infection. Attenuated microbes reproduce in the recipient, typically leading to a more robust and long-lasting immune response than can be obtained through vaccination with killed organisms . For example, vaccine-associated poliomyelitis occurs following administration of approximately 1 of every 2.4 million doses of live polio vaccine 2- killed microorganisms: Killed vaccines have the advantage over 1 attenuated microorganisms in that they pose no risk of vaccine-associated infection. As noted above, killed organisms often provide a weak or short-lived immune response. 3- microbial extracts: Instead of using whole organisms, vaccines can be composed of antigen molecules (often those located on the surface of the microorganism) extracted from the pathogen or prepared by recombinant DNA techniques 4-vaccine conjugates : H. influenza polysaccharide vaccine does not provide protection for children ages 3 to 18 months. Consequently, this organism has, in the past, produced severe infections in this age group. However, by covalent conjugating the Haemophilus polysaccharide to a protein antigen, such as diphtheria toxoid, H. influenzae vaccines produce a robust T cell–dependent antibody response even in 3-month-old infant 5- inactivated toxins (toxoids). Both bacterial and viral pathogens are targeted by these diverse mean. These are derivatives of bacterial exotoxins produced by chemically altering the natural toxin or by engineering bacteria to produce harmless variants of the toxin. 6- DNA vaccines: represent a new approach to vaccination. The proposed mechanism for these vaccines is that the gene for the antigen of interest is cloned into a bacterial plasmid, which is engineered to increase the expression of the inserted gene in mammalian cells. 2 *Types of immune response to vaccines Vaccines containing killed pathogens (such as hepatitis A or the Salk polio vaccine) or antigenic components of pathogens (such as hepatitis B subunit vaccine) do not enter host cells, thereby eliciting a primary B cell mediated humeral response. These antibodies are ineffective in attacking intracellular organisms. By contrast, attenuated live vaccines (usually viruses) do penetrate cells. This results in the production of intracellular antigens that are displayed on the surface of the infected cell, prompting a cytotoxic T-cell response, which is effective in eliminating intracellular pathogens. *The preparation of a vaccine: Production of vaccine can be divided in the following steps: 1. Generation of the antigen The first step in order to produce a vaccine is generating the antigen that will trigger the immune response. For this purpose the pathogen’s proteins or DNA need to be grown and harvested using the following mechanisms: Viruses are grown on primary cells such as cells from chicken embryos or using fertilised eggs (e.g. influenza vaccine) or cell lines that reproduce repeatedly (e.g. hepatitis A) Recombinant proteins derived from the pathogen can be generated either in yeast, bacteria or cell cultures. 2. Release and isolation of the antigen: The aim of this second step is to release as much virus or bacteria as possible. To achieve this, the antigen will be separated from the cells and isolated from the proteins and other parts of the growth medium that are still present. 3. Purification 3 In a third step the antigen will need to be purified in order to produce a high purity/quality product. This will be accomplished using different techniques for protein purification. For this purpose several separation steps will be carried out using the differences in for instance protein size, physico-chemical properties, binding affinity or biological activity. 4. Addition of other components The fourth step may include the addition of an adjuvant, which is a material that enhances the recipient’s immune response to a supplied antigen. The vaccine is then formulated by adding stabilizers to prolong the storage life or preservatives to allow multi-dose vials to be used safely as needed. Due to potential incompatibilities and interactions between antigens and other ingredients, combination vaccines will be more challenging to develop. Finally, all components that constitute the final vaccine are combined and mixed uniformly in a single vial or syringe. 5. Packaging Once the vaccine is put in recipient vessel (either a vial or a syringe), it is sealed with sterile stoppers.. Finally, the vaccine is labeled and distributed worldwide. Routes of administration of vaccine : 1- Intramuscular (IM) injection administers the vaccine into the muscle mass. Vaccines containing adjuvants should be injected IM to reduce adverse local effects. 2-Subcutaneous (SC) injection administers the vaccine into the subcutaneous layer above the muscle and below the skin. 4 3-Intradermal (ID) injection administers the vaccine in the topmost layer of the skin. BCG is the only vaccine with this route of administration. Intradermal injection of BCG vaccine reduces the risk of neurovascular injury. 4-Oral administration of vaccine makes immunization easier by eliminating the need for a needle and syringe. 5-Intranasal spray application of a vaccine offers a needle free approach through the nasal mucosa of the vaccine *Viral vaccines Immunity to viral infection requires an immune response to antigens located on the surface of the viral particles or on virus-infected cells. For enveloped viruses, these antigens are often surface glycoproteins. The main limitation of viral vaccines occurs with viruses that show a genetically unstable antigenicity (that is, they display antigenic determinants that continuously vary, such as with influenza viruses or the human immunodeficiency virus [HIV]. Common viral pathogens for which there are vaccines include the following. A. Hepatitis A Formalin-inactivated whole virus vaccine produces antibody levels in 5 adults similar to those observed following natural infection and is not recommended for children younger than age 2 years because residual anti-hepatitis A passively acquired from the mother may interfere with vaccine immunogenicity. B. Hepatitis B The current vaccine contains recombinant hepatitis surface antigen. C. Varicella zoster This vaccine contains live, attenuated, temperature-sensitive Varicella zoster virus. Its efficacy in preventing chickenpox is approximately 85 to 100 percent in children. D. Polio Vaccine of poliomyelitis is include first the inactivated polio vaccine called (Salk vaccine ,take by injection )and second the live, attenuated(Sabin vaccine, take orally) it provides life-long protection from poliovirus for more than 95 percent of recipient after the primary three-dose series, and 3) it provides early GI immunity . administered polio vaccine have established efficacy in preventing poliovirus infection and paralytic poliomyelitis E. Influenza The traditional “flu shot” vaccine contains formalin-inactivated virus. A live, attenuated influenza vaccine is administered intranasally. F. Measles, mumps, and rubella This combination vaccine contains live, attenuated virus and should be administered to young children prior to entering school. Measles vaccine should also be administered to individuals traveling in endemic areas 6 J. Human papillomavirus vaccine: Human papillomavirus (HPV) vaccine is recommended for routine administration in all children beginning at ages 11 to 12 years. Quadrivalent HPV vaccine is the only vaccine approved for males for protection against genital warts, and either Quadrivalent or bivalent vaccine may be used in females for the protection against cervical cancer and reducing the incidence of genital warts 7