Vaccine 15 09 10

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Jayaraman .VII M.Sc., IbtImmunology

Vaccines And Vaccination

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IntroductionIntroductionVaccination is one of the major contributionsof immunology to medical sciences.Vaccination mainly involves and observes thatindividuals who recovered from someinfectious disease were resistant to subsequent

re-infection.

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E dward Jenner and Louis Pasteur made major contribution and lead a new way inimmunology.Jenner was called as the µ father of

vaccination¶ because he discovered the vaccinefor small pox in the year 1798.

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Definition

DefinitionVaccine;

± A suspension of living organism or inactivatedorganism used as an antigen to confer immunity iscalled vaccine.

Vaccination; ± The administration of an antigen [vaccine] to

stimulate a protective immune response againstaninfectious agent. The term originally refers to

protection against small pox. i.e [vacca-cow].

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Active ImmunityActive ImmunityProtection produced by the person's ownimmune system i.e. in an individual theimmunization procedure involves givingantigen derived from an infectious agent to anindividual so that an immune response is

mounted and resistance to that infection.And it is a permanent one.

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Na tur all y - following exposure to an infection

Medicall

y - by vaccination: Performed either byi.m. injection of killed or attenuated antigens(often with adjuvant) or by ingestion of attenuated live organisms.

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Sources of active ImmunitySources of active Immunity It can be acquired throughN atural infectionVaccines

Attenuated organismsInactivated organismsPurified microbial macromoleculesCloned microbial antigens

Toxoid

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Passive immunityPassive immunityNa tur all y - transplacental transfer of maternal IgG Abs todeveloping fetus; transfer of IgG + IgAAbs in milk during

breast-feeding of newbornMedic all y - injection of immune globulin Performed

prophylactically, either after diagnosis of exposure totoxin/virus or as a short term preventive procedure,it was a Temporary protection And it was an immediate stateof immunity.

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Types of vaccines produces active immunityTypes of vaccines produces active immunity1. Live attenuated vaccines2. Inactivated vaccines

3. Toxoid vaccines4. Subunit vaccines5. Conjugate vaccines6. DN A vaccines7. Recombinant vector vaccines

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Live attenuated vaccinesLive attenuated vaccinesAttenu a ted ± live microbe (usually virus) which has avital function inactivated by heat, chemicals or genetic manipulation.Must replicate to be effectiveImmune response similar to natural infection

Usually effective with one dose.

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Live attenuated vaccinesLive attenuated vaccinesViral - Rabies virus vaccine,

MMR (Measles, Mumps and Rubella),varicella/zoster, yellow fever, rotavirus.

Bacterial - BCG (Bacillus Calmette Guerin vaccine

for Mycobacterium tuberculosis, oral typhoid vaccines

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Inactivated or 'killed' vaccinesInactivated or 'killed' vaccinesCannot replicateGenerally not as effective as live vaccines

Less interference from circulating antibody than livevaccinesGenerally require 3-5 dosesImmune response mostly humoralAntibody titer may diminish with time

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Viral polio, hepatitis A,

influenza*

Bacterial pertussis*, cholera*, plague*

Who le-ce ll va ccines

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Production of live attenuated and inactivated vaccineProduction of live attenuated and inactivated vaccine

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Conjugate or Polysaccharide VaccinesConjugate or Polysaccharide VaccinesN ot consistently immunogenic in childrenyounger than 2 years of ageN o booster responseAntibody with less functional activityImmunogenicity improved by conjugation

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Polysaccharide VaccinesPolysaccharide Vaccinespneumococcal

meningococcalS almonella Typhi (Vi)

Haemophilus influenzae type bpneumococcal

meningococcal

P ure p o lys a cch a ride

C o njug a te p o lys a cc h a ride

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Subunit vaccinesSubunit vaccinesD o NO T use entire virus or bacteria (pathogenicagent)

Use components of pathogenic organism instead of whole organism

Advantage: no extraneous pathogenic particles ieDN A

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E xamples of Subunit VaccinesE xamples of Subunit Vaccines

A. HSVProblem with Traditional vaccine- HSV is oncogenicand thisenvelope glycoprotein D (gD ) elicits Ab responseClone gene for g D into vector E xpress in mammalian cellsTransmembrane proteinmodify gene to remove TM portion

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B . Tubercu l o sis Mycobacterium tuberculosis

antibiotic resistant strainsuse purified extracellular (secreted) proteins as Vaccine

O ther Subunit Vaccines

C. F oo t - a nd-M o ut h Dise a se viruscattle/pigsVP1 capsid viral protein elicits response

-used this protein as Vaccine

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Peptide VaccinesPeptide VaccinesUse discrete portion (domain) of a surface protein as Vaccine

These domains are µepitopes¶antigenic determinants

are recognized by antibodies

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F MD V peptide vaccineF MD V peptide vaccineSolution:

-Use highly immunogenic carrier molecule-HBcAg was a suitable carrier

(Hepatitis Core Protein)-F used peptide DN A with gene for HBcAg-This fusion protein used as Vaccine.

Problem:

-Large quantities of peptide needed to be used to getimmunological response

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D naD na vaccinesvaccinesDN A v a ccin a ti o n is a technique for protecting anorganism against disease by injecting it withgenetically engineered DN A to produce an

immunological response .N ucleic acid vaccines are still experimental, and have

been applied to a number of viral , bacterial and parasitic models of disease, as well as to severaltumour models.DN A vaccines have a number of advantages over conventional vaccines, including the ability to induce awider range of immune response types.

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Current useCurrent use bird flu DN A vaccine

veterinary DN A vaccine to protect horses from West N ile virus

DN A vaccination againstmultiple sclerosis wasreported as being effective.

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Adv a nt a ges Dis a dv a nt a gesy Antigen presentation by both MHC class

I and class II molecules [1]

y Able to polarise T-cell help toward type1 or type 2 [1]

y Immune response focused only onantigen of interest

y E ase of development and production [1]

y Stability of vaccine for storage andshipping

y Cost-effectiveness

y lon -term ersistence of immuno en [2]

y Limited to protein immunogens (notuseful for non-protein based antigenssuch as bacterial polysaccharides)

y Risk of affecting genes controlling cellgrowth

y Possibility of inducing antibody production against DN A

y Possibility of tolerance to the antigen(protein) produced

y Potential for atypical processing of bacterial and parasite proteins [1]

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Table 3. Advantages and disadvantages of commonly used DN A vaccine delivery methods

Met ho d of De l ivery Adv a nt a ge Dis a dv a nt a ge

Intramuscular or Intradermalinjection

y N o special delivery mechanism

y Permanent or semi-permanent expression

y pDN A spreads rapidly throughout the body

y Inefficient site for uptake due to morphology of muscle tissue

y Relatively large amounts of DN A used

y Th1 response may not be the response required

Gene Guny DN A bombarded directly into cells

y Small amounts DN A

y Th2 response may not be the response required

y Requires inert particles as carrier

Jet injection

y N o particles required

y DN A can be delivered to cells mm to cm below skinsurface

y

Significant shearing of DN A after high-pressureexpulsion

y 10-fold lower expression, and lower immuneresponse

y Requires large amounts of DN A (up to 300 g)

Liposome-mediated delivery

y High levels of immune response can be generated

y Can increase transfection of intravenously delivered pDN A

y Intravenously delivered liposome- DN A complexescan potentially transfect all tissues

y

Toxicityy Ineffectiveness in serum

y Risk of disease or immune reactions

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Development of new vaccines

Development of new vaccinesVaccines most desirable method of disease control

E arly successful vaccines cultured in animalsWith cell culture- could make vaccines that would notgrow on anything but human cellsSome vaccines do not need cell culture- recombinantvaccines and DN A vaccinesPlant potential source for vaccinesIn future- possibility for vaccines to treat addiction,Alzheimer's, disease and cancer

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THANK YOUTHANK YOU

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Vaccine 15 09 10