A vaccine is a biological preparation that improves immunity to a particular disease.

ƒ A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins. ƒ The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "recognize" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.
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Vaccination is also called active immunization because the immune system is stimulated to develop its own immunity against the pathogen. ƒ Passive immunity, in contrast, results from the injection of antibodies formed by another animal (e.g., horse, human) which provide immediate, but temporary, protection for the recipient.
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The terms vaccination and vaccine derived from the work of Edward Jenner who, over 200 years ago, showed that inoculating people with material from skin lesions caused by cowpox (L. vaccinus, of cows) protected them from the highly contagious and frequently fatal disease smallpox.

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Since Jenner's time, the term has been retained for any preparation of dead or weakened pathogens, or their products, that when introduced into the body, stimulates the production of protective antibodies or T cells without causing the disease. In molecular terms, the goal is to introduce harmless antigen(s) with epitopes that are also found on the pathogen.

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Vaccine production has several stages. First, the antigen itself is generated. 
Viruses are grown either on primary cells such as

chicken eggs (e.g., for influenza), or on continuous cell lines such as cultured human cells (e.g., for hepatitis A)  Bacteria are grown in bioreactors (e.g., Haemophilus influenzae type b) 

a recombinant protein derived from the viruses or

bacteria can be generated in yeast, bacteria, or cell cultures.
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After the antigen is generated, it is isolated from the cells used to generate it. 
A virus may need to be inactivated, possibly with

no further purification required  Recombinant proteins need many operations involving ultrafiltration and column chromatography.

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Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed. 
adjuvant enhances the immune response of the

antigen  stabilizers increase the storage life,  and preservatives allow the use of multidose vials.

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Beside the active vaccine itself, the following excipients are commonly present in vaccine preparations: 
Aluminum salts or gels are added as adjuvants. Adjuvants

are added to promote an earlier, more potent response, and more persistent immune response to the vaccine; they allow for a lower vaccine dosage.  Antibiotics are added to some vaccines to prevent the growth of bacteria during production and storage of the vaccine.  Egg protein is present in influenza and yellow fever vaccines as they are prepared using chicken eggs. Other proteins may be present. 

Formaldehyde is used to inactivate bacterial products for

toxoid vaccines. Formaldehyde is also used to kill unwanted viruses and bacteria that might contaminate the vaccine during production.  Monosodium glutamate (MSG) and 2-phenoxyethanol are used as stabilizers in a few vaccines to help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or humidity.  Thimerosal is a mercury-containing preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria.

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ATTENUATED VIRUSES AND BACTERIA:Attenuation often can be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants that are better suited to growth in abnormal cultre conditions and are therefore less capable of growth in normal host . For example, an attenuated strain of mycobacterium bovis called BCG was developed by growing M.bovis on a medium

Conatining increasing concentartion of Bile. ADVANTAGES ƒ prolonged exposure to the individual epitopes on the attenuated organisms, resulting in increased immunogencity. ƒ The ability to replicate within host cells make them particularly sutaible for inducing a cell mediated response. DISADVANTAGE ƒ They will revert to virulent form.

Another common approach in vaccine production is inactivation of the pathogen by heat or chemical means so that no longer capable of replication in the host. Its critically important to maintain the structure of epitopes on surface antigens during inactivation.Heat inactivation is generally unstisfactory because it causes extensive denaturation of proteins. Chemical inacativation with formaldehyde or various

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alkylating agents has been successful.The salk poio vaccine is produced by formaldehyde inactivation. They require repeated boosters to maintain the immune status of the host.

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Some of the risks associated with attenuated or killed whole organism vaccinces can be avoided with vaccines that consist of specific, purified macromolecules derived from pathogens. Inactivated exotoxins Capsular polysaccharides Recombinant microbial antigens

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The current vaccine for streptococcus pneumoniae, which causes pneumococcal pneumonia, consists of 23 antigenically different capsular polysaccharides. The vaccines induces formation of opsonizing antibodies. Vaccine for Neisseria meningitidis, a common cause of bacterial meningitis, also consists of purified capsular polysaccharides.

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Limitation:- Their inability to activate T helper cells. They activate B cells, resulting in IgM production. To solve this problem polysacchsride protein conjugate considerabily more immunogenic than the polysaccharide, because it activates T helper cells wich enables class switching from IgM to IgG.

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Diptheria and tetanus vaccines can be made by purifiying the bacterial exotoxin and then inactivating the toxin with formaldehyde to form a toxoid. Vaccination with the toxoid induces antitoxoid antibodies. Which are also capable of binding to the toxin and neutralizing its effects.

This type of vaccines have been developed by cloning the gene for the major surface antigen of hepatitis B virus(HBsAg) and expressing in yeast cells. The recombinant yeast cells are grown in the large fermenters, and HBsAg accumulates in the cells. ‡ The yeast cells are harvested and disrupted by high pressure, releasing the recombinant HBsAg which is then purified by conventional biochemical techniques.This recombinant hepatits B vaccine has been shown to induce the production of protective antibodies.
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