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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