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A vaccine is a biological preparation thatimproves immunity to a particular disease.

A vaccine typically contains an agent that

resembles a disease-causing microorganism, andis often made from weakened or killed forms ofthe microbe or its toxins.

The agent stimulates the body's immune system

to recognize the agent as foreign, destroy it, and"recognize" it, so that the immune system canmore easily recognize and destroy any of thesemicroorganisms 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.

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 peoplewith material from skin lesions caused by

cowpox (L. vaccinus, of cows) protected them

from the highly contagious and frequentlyfatal disease smallpox.

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Since Jenner's time, the term has been retainedfor any preparation of dead or weakened

pathogens, or their products, that whenintroduced into the body, stimulates the

production of protective antibodies or T cellswithout causing the disease. In molecular

terms, the goal is to introduce harmlessantigen(s) with epitopes that are also found onthe pathogen.

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Vaccine production has several stages.

First, the antigen itself is generated.

Viruses are grown either on primary cells such aschicken 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)

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a recombinant protein derived from the viruses orbacteria can be generated in yeast, bacteria, or cellcultures.

After the antigen is generated, it is isolatedfrom the cells used to generate it.

A virus may need to be inactivated, possibly withno further purification required

Recombinant proteins need many operationsinvolving ultrafiltration and columnchromatography.

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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 arecommonly present in vaccine preparations:

Aluminum salts or gels are added as adjuvants. Adjuvantsare added to promote an earlier, more potent response, andmore persistent immune response to the vaccine; they allowfor a lower vaccine dosage.

Antibiotics are added to some vaccines to prevent thegrowth 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. Otherproteins may be present.

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Formaldehyde is used to inactivate bacterial products fortoxoid vaccines. Formaldehyde is also used to kill unwantedviruses 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 vaccineremain unchanged when the vaccine is exposed to heat,light, acidity, or humidity.

Thimerosal is a mercury-containing preservative that isadded to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmfulbacteria.

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ATTENUATED VIRUSES AND BACTERIA:-

Attenuation often can be achieved by growing apathogenic 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 aretherefore less capable of growth in normal host . For

example, an attenuated strain ofmycobacterium boviscalled BCG was developed by growing M.bovis on amedium

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Conatining increasing concentartion of Bile.ADVANTAGES prolonged exposure to the individual epitopes

on the attenuated organisms, resulting inincreased immunogencity.

The ability to replicate within host cells makethem particularly sutaible for inducing a cell

mediated response.DISADVANTAGE They will revert to virulent form.

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Another common approach in vaccineproduction is inactivation of the pathogen byheat or chemical means so that no longercapable of replication in the host. Its criticallyimportant to maintain the structure of epitopeson surface antigens during inactivation.Heatinactivation is generally unstisfactory because itcauses extensive denaturation of proteins.Chemical inacativation with formaldehyde orvarious

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alkylating agents has been successful.The salk

poio vaccine is produced by formaldehydeinactivation.

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 antigenicallydifferent capsular polysaccharides. The

vaccines induces formation of opsonizingantibodies.

Vaccine for Neisseria meningitidis, acommon 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 Thelper cells wich enables class switching fromIgM 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 toform a toxoid.

Vaccination with the toxoid induces anti-toxoid antibodies. Which are also capable of

binding to the toxin and neutralizing itseffects.

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This type of vaccines have been developed bycloning the gene for the major surface antigen ofhepatitis B virus(HBsAg) and expressing in yeast

cells. The recombinant yeast cells are grown inthe large fermenters, and HBsAg accumulates inthe cells.

The yeast cells are harvested and disrupted byhigh pressure, releasing the recombinant HBsAgwhich is then purified by conventionalbiochemical techniques.This recombinanthepatits B vaccine has been shown to induce theproduction of protective antibodies.