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LOGO

11.VACCINE

TIANA MILANDA

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What is a vaccine ?

A preparation of bacteria, viruses,

parasites designed to elicit animmune response, therebyproviding protective immunityagainst a potential pathogen.

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Passive vs ActiveImmunity

Passive Immunity Immunity due by thepresence in theirtissues of antibody orprimed lymphocytes

derived from anotherimmune individual.

Active Immunity Protection due todevelopment of an

immune response in anindividual followingstimulation withantigen, e.g. in avaccine or duringinfection.

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Passive Immunization

Transfer of preformed antibodies or primedlymphocytes to a new recipient. Usually, horse serumor pooled human sera are used.

Transfer can occur naturally, through placenta, milkor colostrum (e.g. diphtheria, tetanus, rubeola,rubella, mumps, polio)

Transfer can occur manually, via injection ofantibodies into recipient

Passive immunization is performed in the followingsituations:

Recepient has congenital or acquired B cell defects When exposure is likely, or when time doesnt permit active

immunization

When disease is already present (e.g. tetanus, spider/snake bites)

Risks include anti-isotype or anti-allotype responses

in recipients

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Active Immunization

Intentional induction of protective immunityand immunological memory

Can be mediated by infection withmicroogranism, or vaccination

Vaccinations frequently require boosters,subsequent vaccinations to boost theimmune response to a particular pathogen:

Passively acquired maternal antibodies may interferewith vaccination process

Multiple exposures may be necessary to adequatelyimmunize against all strains/epitopes

Memory T cell population may decline with age

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Fig. 18-3

Immune Response

To Polio Vaccine

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Immunization schedule for infants and children

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History

Greek physicians noticedthat people who survivedsmallpox never got itagain.

The insight: Becominginfected by certaindiseases gives immunity.

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Smallpox

Mummies

China/India Crusaders

West Europe: fatality rate 25%

History changed:

Cortes

Louis XIV

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Smallpox

Vaccination

Jenner 1796 :Cowpox/Swinepox

1800s : compulsory

childhood vaccination 1930s : last natural UK

case

1940s : last natural US case 1958 : WHO program October 1977: Last case

(Somalia)

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Types Of Vaccines

Whole Organism Vaccines Attenuated (non-virulent) viral or bacterial vaccines

Inactivated (killed) viral or bacterial vaccines

Purified Macromolecule Vaccines

Toxoid Vaccines (e.g. tetanus, diphtheria)

Polysaccharide Vaccines (e.g. S. pneumoniae, Hib)

Recombinant Antigen Vaccines (e.g. HBsAg)

Recombinant Vector Vaccines

DNA Vaccines

Synthetic Peptide Vaccines

Multivalent Subunit Vaccines

Li Att t d V i

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Live Attenuated Vaccines

Attenuated (weakened) form of the

"wild" virus or bacteriumViral measles, mumps,

rubella, vaccinia,varicella/zoster,

yellow fever, rotavirus,intranasal influenza,oral polio (Sabin)

Bacterial BCG (TB), oral

typhoid

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Inactivated Vaccines

Virulent pathogen is inactived by chemical

or irradiations

Viral polio (Salk),

hepatitis A,rabies, influenza

Bacterial pertussis,typhoid, cholera

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Sabin Polio Vaccine Attenuated by passage in foreign host (monkey kidney

cells)

Selection to grow in new host makes virus less suited tooriginal host

Grows in epithelial cells, does not grow in nerves

50% vaccinees feces, 50% contacts

Vaccine-associated cases: revertants

1 In 4,000,000 vaccine infections paralytic polio

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Salk Polio Vaccine

Formaldehyde-fixed

No reversion

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Polio Vaccine

Why use the Sabin vaccine?

Local immunity: vaccine virus just like naturalinfection

Stopping replication in G.I. tract stops viralreplication TOTALLY

No problem with selective inactivation

Life-long immunity

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Reciprocalvirusantibody

titer

512

128

32

8

2

1

SerumIgG

SerumIgG

Serum IgM SerumIgM

Nasal andduodenal IgA

NasalIgASerum

IgA

SerumIgA

DuodenalIgA

DaysVaccination Vaccination

4

8

4896 96

Killed(Salk)Vaccine

Live

(Sabin)Vaccine

Live virus generates a more complete immune response

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Types Of Vaccines



Purified Macromolecule Vaccines Polysaccharide Vaccines (e.g. S. pneumoniae, Hib)




DNA Vaccines



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Clone gene from virus or bacteriaand express this protein antigen in

yeast, bacteria or mammalian cellsin culture

Recombinant Antigen Vaccines

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Recombinant Antigen Vaccines

Pluses

Easily manufactured and often relatively stable

Cannot revert to recreate pathogen

Minuses Poorly immunogenic

Post-translational modifications

Poor T cell response

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Types Of Vaccines



Purified Macromolecule Vaccines Polysaccharide Vaccines (e.g. S. pneumoniae, Hib)




DNA Vaccines



R bi V V i

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Clone gene from virus or bacteria into genome of anothervirus (adenovirus, canary pox, vaccinia)

And use this live virus as vaccine

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Recombinant Vector VaccinesPluses

Infects human cells but some do not replicate Better presentation of antigen

Generate T cell response

Minuses

Can cause bad reactions

Can be problems with pre-exisiting immunity to virus

Often can only accommodate one or two antigens

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Fig. 18-6

DNA

Vaccines

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DNA Vaccines Plasmids are easily manufactured in largeamounts

DNA is very stable. DNA resists temperatureextremes so storage and transport

DNA sequence can be changed easily in the

laboratory. This means that we can respond tochanges in the infectious agent By using the plasmid in the vaccine to code forantigen synthesis, the antigenic protein(s) that are

produced are processed in the same way as theproteins of the virus.

Mixtures of plasmids could be used that encodemany protein fragments from a virus/viruses a

broad spectrum vaccine

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DNA Vaccines

Possible Problems

Potential integration of plasmid into host genomeleading to insertional mutagenesis

Induction of autoimmune responses (e.g.pathogenic anti-DNA antibodies)

Induction of immunologic tolerance (e.g. where

the expression of the antigen in the host may leadto specific non-responsiveness to that antigen)

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antibody

Synthetic peptide vaccines

Anti-idiotype vaccine

epitope

Antibody with

epitope bindingsite

Virus

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antibody

Make antibodyagainst antibodyidiotype

Anti-idiotypeantibody

Anti-idiotypeantibody mimicsthe epitope


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Anti-anti-idiotypeantibody

Antibody to anti-idiotypeantibody

Binds and neutralizesvirus




Use as vaccine


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Multivalent

SubunitVaccines

Fig. 18-7

Multivalent subunit vaccine

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Influenza Vaccine

Trivalent

Efficacy

Immunity

Schedule

Type A (2) and type B (1)

Varies depending on circulatingstrain, age, and underlyingillness

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Ideal Vaccine

Safe

InexpensiveHeat-stable

Oral administration

Effective in all ages

Single dose

All strains sensitive

Induces systemic

and mucosalimmunity CTL andantibody

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What knowledge is needed toproduce a vaccine ?

1. Understand lifecycle of pathogen find best target stage.

2. Understand immune mechanisms stimulatedby parasite humoral /cellular response ?

3. Understanding the incubation period of thepathogen.

A short incubation period (e.g. influenza)results in symptoms before memory cells are

activated. Circulating antibodies are importantin these instances.

Longer incubation periods (e.g. polio) allowmemory cells to become activated prior to

onset of symptoms

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HIV: Virion (Virus Particle)

gp120

gp41

viral e nvelopeglycoproteins

lipid

membrane ofenvelope

(host derive d)

matrix (p17)

viral core(p24)

reverse

transcriptase

viral RNA (ss)(2 copie s)

HIV Virion Structure

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HIV Lifecycle

T Cell

CD4

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X

Reverse TranscriptionInhibitors

Protease Blockers

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HIV Vaccine Approaches

Protein subunit

Synthetic peptide

Naked DNA

Inactivated Virus

Live-attenuatedVirus

Live-vectored Vaccine

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Old Technology:

Grow in animals (vacciniain calves for smallpox;rabbit brains for rabies)

Simple bacterial culture

(Cholera vibrio) theninactivation

Grow in eggs (influenza,vaccinia) then inactivate

>100 million eggs used forinfluenza in the USA every year

Vaccine Technology

i h l

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Vaccine Technology

Newer Technology:

Mammalian cell culture: live and killedvaccines

Subunit vaccines:

From serum (HBV) or virus / bacterial disruption Made via recombinant DNA technology

Recombinant vaccine vectors

DNA vaccines

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Antibody to anti-idiotypeantibody

Binds and neutralizesvirus




Use as vaccine

Vaccine Technology

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Thank you!

Documents

11. Vaksin