Vaccine & Vaccination

7/31/2019 Vaccine & Vaccination

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Vaccine & VaccinationVeterinary Medicine

Brawijaya University


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Antibody/ Immunoglobulin

Is family of structurally related glycoproteinsproduced in membrane-bound or secreted form

by B lymphocytes (mature B cells). Membrane-bound antibodies serve as receptors

that mediate the antigen-triggered activation ofB cells (IgM & IgD)

Secreted antibodies functions as mediators ofspecific humoral immunity by engaging variouseffectors mechanisms that serve to eliminate thebound


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Fab

The antigen-binding regions of antibody molecules arehighly variable, and any one individual produces up to109 different antibodies, each with distinct antigenspecificity


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ANTIGENS

An antigen is a foreign or recognized as foreignsubstances, that may be specifically bound by anantibody molecule or T cell receptor

Molecules that stimulate immune responses arecalled immunogens

Macromolecular antigens contain multiple epitopesor determinants, each of which may be recognizedby an antibodySpecificity of an antigen is on its epitopes

Linear epitopes of protein antigens may be formed

by a sequence of adjacent amino acids, andconformational determinants may be formed byfolding of polypeptide chain.

Polyvalent antigens contain multiple identicalepitopes to which identical antibody molecules can

bind.


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Antibodies can bind to two or in case of IgM, upto 10 identical epitopes simultaneously, leadingto enhance avidity of antibody-antigeninteraction. The relative concentrations ofpolyvalent antigens and antibodies may favor

the formation of immune complexes that maydeposit in tissues and cause damage


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Requirements for an antigen

Foreign substance for the body

Have high molecular weight (> 10.000 Da)

Have complex chemical arrangement

Protein

Glycoprotein

Lipoprotein

Polysaccharide Possess determinant antigen/epitopes


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Intrinsic properties & Extrinsic factors influencing the

immunogenicity of proteins

Parameter Increasedimmunogenicity Decreasedimmunogenicity

Size Large Small ( MW Intraperitoneal > Intravenous or

Intragastric

Composition Complex Simple

Form Particulate Soluble

Denatured Native

Similarity to self protein(level of foreignness) Multiple differences Few Differences

Adjuvants Slow release Rapid release

Bacteria No bacteria

Interaction with host

MHC

Effective Ineffective


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The dose of antigen used in initial immunization

affects the primary & secondary antibody

responsesPrimary Immunization withdifferent dose of antigen

Secondary Immunizationwith single dose of antigen

Antibody responses

Antigen dose

Antibody responses

highzonetole-rance

low-zone

tole-rance

Antigen dose


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Booster

Firstimmunization

Repeatimmunization

Days after antigen exposure Days after antigen exposure

Am

ountofantibody


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Primary and secondary humoral immune

responsesFeature Primary responses Secondary responses

Time lag afterimmunization

Usually 5 10 days Usually 1 3 days

Peak response Smaller Larger

Antibody isotype Usually IgM>IgG Relative increase inIgG and under certainsituation s in IgA or IgE

Antibody affinity Lower average affinity,more variable

Higher average affinity(affinity maturation)

Induce by All immunogens Only protein antigens

Requiredimmunization

Relatively high doses ofantigens, optimally withadjuvants (for proteinantigen)

Low doses of antigens,adjuvants may not benecessary


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Type of antigen

1. Complete antigen Immunogenic

Induce immunocompetent cells to produce antibodies

Reactive

The antibodies react specifically to the antigen Ex: Protein, lipoprotein, microbial antigen, etc

2. Incomplete antigen (hapten)

Low molecular weight

Immunogenicity : -

Reactivity : +

Hapten-binding protein (protein carrier) CompleteAntigen

Ex: Antibiotics, drugs, cosmetics


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Antigen classification base on:

Genetic

Antigen histocompatibility organs transplantation

Auto-Antigen auto immune diseases Iso-Antigen :

Individually antigen in a species (blood group)

Allo-Antigen

Totally different antigen between organism


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Dependency to T cell/ thymus T cell/ thymus dependent antigen (terbalik)

Via B cell to induce antibody

LPS, Poly-L-Lysine

T cell/thymus independent antigen Antigen protein

To produce immunity (humoral or and cellular) haveto presented by APC to T cell


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VACCINE

Edward Jenners (1796) vaccination againstsmallpox

Disease Max numberof cases (year)

Numbercases in 2004

Percentchange

Diphtheria 206.939 (1921) 0 -99,99Measles 895,134 (1941) 37 -99,99

Mumps 152.209 (1968) 236 -99,90

Pertussis 265.269 (1934) 18.957 -96,84

Polio 21.269 (1952) 0 -100,00Rubella 57.686 (1969) 12 -99,98

Tetanus 1.560 (1923) 26 -98,33

Haemophilus influenzae type B 20.000 (1984) 16 -99,92

Hepatitis B 26.611 (1985) 6.632 -75,08


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The success of active immunization in

eradicating infectious disease is dependent

on numerous factors:

The infectious agent does not establish as

latency Does not highly variable of antigenic structure Does not interfere by the host immune response Vaccines are most effective against infections

that limited to one species host

Higher antibodies, long-live effectors cells &memory cells


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Attenuated & Inactivated Vaccines

Composed of intact non pathogenic microbes: Its virulence is attenuated

Killing

Retaining its immunogenicity The great advantages:

Elicit all innate & adaptive immunity as same asthe pathogenic microbes done

Inducing protective immunity Live attenuated usually more effective

Viral vaccine often induce long-lasting specificimmunity


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Purified Antigen (Subunit) Vaccines

Composed of:

Purified antigens from microbes

Toxin

Usually administrated with an adjuvant Toxin induce strong antibody responses

LPS antigens induce low-affinity antibodyresponses (T cell independent antigen)

AgainstPneumococcal & H influenzae


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Conjugate vaccines induce high-affinity antibody

responsesComposed of:

Poorly immunogenic antigens

Coupling to protein

Ex: hapten-carrier conjugates to pneumococcus,H. influenzae, meningococcus

Purified protein induce high-affinity antibody

Stimulate Th & antibody response Not recognized efficiently by class I-restricted

CD8+ T cells


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Synthetic Vaccines Identify the most immunogenic microbial

antigens or epitopes, to synthesize these in thelaboratory synthetic antigenssynthetic vaccines

Recombinant DNA technology protein inlarge quantities vaccine made from

recombinant DNA-derived antigens Ex: hepatitis virus, herpes simplex virus, foot-and-

mouth disease virus


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Live Viral Vectors

A vaccine development is to introduce genesencoding microbial antigens in a noncytophatic(not pathogenic) virus and to infect individuals

with this virus The great advantage of viral vectors is induce:

Complement lyses the target of vaccine

CTL responses kill the infected host cell

Induce both humoral & cell-mediated immunity


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DNA Vaccines

An interesting method of vaccination was developed onthe basis of an unexpected observation Inoculation of a plasmid containing complementary

DNA (cDNA) encoding a protein antigen leads to strongand long-lived humoral and CMI responses to theantigen.

It is likely that APC are transfected by plasmid and thecDNA is transcribed translates immunogenicprotein that elicits specific responses

Vaccine DNA-encoded viral protein eliciting strongCTL responses

Vaccine DNA-encoded bacterial protein enhancesadaptive immunity


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Multivalent vaccines

Problems : The vaccine poorly immunogenic

Induce either humoral or CMI

Approach:

1. SMMA (solid matrix-antibody antigen)

Monoclonal antibody attaching to particulate solidmatrices + saturating the monoclonal antibody

with desired antigens possible bind mixturepeptide/protein contain immunodominantepitopes for T and B cells


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2. Desired antigen incorporate into proteinmicelles/ lipid vesicles (liposomes)/immunostimulating complexes (ISCOMs), usingdetergents

- Micelles formed by mixing protein antigens indetergent and then removing the detergent

- Liposome is lipid bilayer

- ISCOM is lipid carrier

3. Membrane protein from various pathogenincorporated into micelles, liposome or ISCOM


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Adjuvant

Adjuvants (latin: adjuvare, to help) aresubstances that when mixed with an antigen andinjected with it, enhance the immunogenicity of

the antigen. Protect the antigen (vaccine)

Non Antigenic material

Used to boost the immune response when: The antigen has low immunogenicity

Only small amounts of antigen


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Adjuvant:

Elicit innate immune responses Increase costimulators signals

Induce granuloma formation

Increase cytokines, such as IL-12 stimulate

growth & differentiation of immunocompetentcells

Stimulate lymphocyte proliferation nonspecifically


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Mode of action of some commonly used adjuvants

Postulated mode of action

adjuvant Prolongsantigenpersistence

Enhancecostimulatorysignal

Inducegranulomaformation

Stimulateslymphocytesnonspecifically

Freunds incompleteadjuvant

+ + + -

Freunds completeadjuvant

+ ++ ++ -

Aluminum potassiumsulfate (alum)

+ ? + -

M. tuberculosis - ? + -

B. pertussis - ? - +

LPS - + - +

Synthetic polynucleo-

tides (poly IC/poly AU)

- ? - +


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Passive Immunization By transfer of specific antibodies Most commonly used for rapid treatment of

potentially fatal disease caused by toxin Tetanus Rabies

Diphtheria Snake venom Naturally transfer maternal antibodies across

placenta to the developing fetus Passive immunity is short-lived, because:

Host does not respond to immunization Protection lasts only as long as the injected antibody

persists Does not induce memory not protected against

subsequent exposure toxin

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