Immunization:
Vaccinology
• Immunization,is the process by which an
individual's immune system becomes
fortified against an agent (known as
the immunogen).
• Immunization is done through various
techniques, most commonly vaccination
Vaccinology
 The science or methodology of vaccine development .
 Vaccine: A vaccine is a biological preparation that improves
immunity to a particular disease.
 A vaccine typically contains an agent that resembles a disease-
causing microorganism, and is often made from weakened or
killed forms of the microbe.
 The agent stimulates the body's immune system to recognize
the agent as foreign, destroys it, and "remembers" it, so that the
immune system can easily recognize and destroy any of these
micro-organisms that it encounters later.
Properties of an ideal vaccine
 Provide long lasting immunity.
 Should induce both humoral and cellular immunity.
 Should not induce autoimmunity or hypersensitivity.
 Should be inexpensive to produce, easy to store and administer.
 Vaccines must also be perceived to be safe.
 The vaccine vial may contain relevant antigen, adjuvant (usually
alum), preservatives and/or traces of protein derived from the cells
in which the vaccine agent was cultured e.g. egg protein.
Types of Vaccines
 Killed
 Attenuated
 Toxiod
 Subunit
 Peptide vaccines
 Conjugate
 DNA
 Recombinant Vector Vaccines
 Anti-idiotypic Vaccine
Live Attenuated Vaccines
• Live, attenuated vaccines contain a version of the living microbe
that has been weakened in the lab so it can’t cause disease.
• Because a live, attenuated vaccine is the closest thing to a natural
infection, these vaccines are good “teachers” of the immune system:
• They elicit strong cellular and antibody responses and often confer
lifelong immunity with only one or two doses.
Disadvantages
• It is the nature of living things to change, or mutate, and the organisms used
in live, attenuated vaccines are no different.
• The remote possibility exists that an attenuated microbe in the vaccine could
revert to a virulent form and cause disease.
• Also, not everyone can safely receive live, attenuated vaccines. For their
own protection, people who have damaged or weakened immune systems—
because they have undergone chemotherapy or have HIV, for example—
cannot be given live vaccines.
 Another limitation is that live, attenuated vaccines usually need to
be refrigerated to stay potent.
 If the vaccine needs to be shipped overseas and stored by health
care workers in developing countries that lack widespread
refrigeration, a live vaccine may not be the best choice.

Killed Vaccines
 Such vaccines are more stable and safer than live vaccines:
 The dead microbes can’t mutate back to their disease-causing state.
 Inactivated vaccines usually don’t require refrigeration, and they can be easily
stored and transported in a freeze-dried form, which makes them accessible to
people in developing countries.
 Most inactivated vaccines, however, stimulate a weaker immune
system response than do live vaccines.
 So it is likely to take several additional doses, or booster shots, to maintain a
person’s immunity.
 This could be a drawback in areas where people don’t have regular
access to health care and can’t get booster shots on time.
Subunit Vaccines
 Instead of the entire microbe, subunit vaccines include only the antigens
that best stimulate the immune system.
 In some cases, these vaccines use epitopes—the very specific parts of the
antigen that antibodies or T cells recognize and bind to.
 Because subunit vaccines contain only the essential antigens and not all
the other molecules that make up the microbe, the chances of adverse
reactions to the vaccine are lower.
 Subunit vaccines can contain anywhere from 1 to 20 or more antigens.
 Of course, identifying which antigens best stimulate the immune system
is a tricky, time-consuming process.
Subunit vaccines can be made in one of two ways:
 The microbe can be grown in the laboratory and then chemicals are
used to break it apart and gather the important antigens.
 The antigen molecules can be manufactured from the microbe using
recombinant DNA technology. Vaccines produced this way are called
“recombinant subunit vaccines.”
 A recombinant subunit vaccine has been made for hepatitis B virus.
Scientists inserted hepatitis B virus genes that code for important
antigens into common baker’s yeast.
 The yeast then produced the antigens, which the scientists collected
and purified for use in the vaccine.
 HBsAg, HBxAg, etc.
Advantages:
• They can safely be given to immunosuppressed people.
• They are less likely to induce side effects.
Disadvantages:
• Antigens may not retain their native conformation, so that antibodies
produced against the subunit may not recognize the same protein on
the pathogen surface.
• Isolated protein does not stimulate the immune system as well as a
whole organism vaccine.
Peptide vaccines
• Peptide vaccine consists of those peptides from the microbial antigen that
stimulates protective immunity.
• Synthetic peptides are produced by automated machines rather than by
microorganisms.
• Peptide immunogenicity can be increased by giving lipid micelles that
transport the peptides directly into the cytoplasm of dendritic cells for
presentation on Class I MHC.
• Injected peptides, which are much smaller than the original virus protein,
induce an IgG response.
• Example: spf66 anti-malarial vaccine
Advantages:
• If the peptide that induces protective immunity is identified, it can be
synthesized easily on a large scale.
• It is safe and can be administered to immunodeficient and pregnant
individuals.
Disadvantage:
• Poor antigenicity. Peptide fragments do not stimulate the immune system as
whole organism vaccine.
• Since peptides are closely associated with HLA alleles, some peptides may
not be universally effective at inducing protective immunity.
Toxoid Vaccines
 A vaccine made from a toxin (poison) that has been made
harmless but that elicits an immune response against the toxin
 Based on the toxin produced by certain bacteria (e.g. tetanus or
diphtheria).
 These vaccines are used when a bacterial toxin is the main cause
of illness.
 Bacterial toxins are inactivated by treating them with formalin,
a solution of formaldehyde and sterilized water.
 Such “detoxified” toxins, called toxoids, are safe for use in
vaccines.
 When the immune system receives a vaccine containing a
harmless toxoid, it learns how to fight off the natural toxin.
 The immune system produces antibodies that lock onto and
block the toxin.
 Vaccines against diphtheria and tetanus are examples of toxoid
vaccines.
Conjugate Vaccines
 A conjugate vaccine is created by covalently attaching a poor
(polysaccharide organism) antigen to a carrier protein (preferably
from the same micro-organism), thereby conferring the
immunological attributes of the carrier on the attached antigen.
 This technique for the creation of an effective immunogen is most
often applied to bacterial polysaccharides for the prevention of
invasive bacterial disease.
 Polysaccharide coatings disguise a bacterium’s antigens so that the
immature immune systems of infants and younger children can’t
recognize or respond to them.
Conjugate Vaccines-1
 Conjugate vaccines are a special type of subunit vaccine to get
around this problem.
 When making a conjugate vaccine, scientists link antigens or
toxoids from a microbe that an infant’s immune system can
recognize to the polysaccharides.
 The linkage helps the immature immune system to react to
polysaccharide coatings and defend against the disease-
causing bacterium.
 The vaccine that protects against Haemophilus influenzae type B
(Hib) is a conjugate vaccine and other e.g are Pneumoccocal
Vaccine and Meningococcal Vaccine
DNA Vaccines
 A DNA vaccine against a microbe would evoke a strong
antibody response to the free-floating antigen secreted by cells,
and the vaccine also would stimulate a strong cellular response
against the microbial antigens displayed on cell surfaces.
 DNA vaccines can not cause the disease because they do not
contain the microbe, just copies of a few of its genes.
 In addition, DNA vaccines are relatively easy and inexpensive
to design and produce.
 Naked DNA vaccines are being tested in humans including
those against the viruses that cause influenza and herpes.
Advantages:
• DNA is very stable, it resists extreme temperature and hence storage and transport are easy.
• A DNA sequence can be changed easily in the laboratory.
• The inserted DNA does not replicate and encodes only the proteins of interest.
• There is no protein component and so there will be no immune response against the vector
itself.
• Because of the way the antigen is presented, there is a cell-mediated response that may be
directed against any antigen in the pathogen.
Disadvantages:
• Potential integration of DNA into host genome leading to insertional mutagenesis.
• Induction of autoimmune responses: anti-DNA antibodies may be produced against
introduced DNA.
• Induction of immunologic tolerance: The expression of the antigen in the host may lead to
specific nonresponsiveness to that antigen.
Recombinant Vector Vaccines
• Recombinant vector vaccines are experimental vaccines similar to DNA
vaccines, but they use an attenuated virus or bacterium to introduce
microbial DNA to cells of the body.
• “Vector” refers to the virus or bacterium used as the carrier.
• In nature, viruses bind to cells and inject their genetic material into
them.
• In the lab, scientists take advantage of this process.
• The carrier viruses then transport that microbial DNA to cells.
• Recombinant vector vaccines closely mimic a natural infection and
therefore do a good job of stimulating the immune system.
 Attenuated bacteria also can be used as vectors.
 In this case, the inserted genetic material causes the bacteria to
display the antigens of other microbes on its surface.
 In effect, the harmless bacterium mimics a harmful microbe,
provoking an immune response.
 Researchers are working on both bacterial and viral-based
recombinant vector vaccines for HIV, rabies, and measles.
Anti-idiotypic Vaccine
 An antigen binding site in an antibody is a reflection of the three-
dimensional structure of part of the antigen (epitope).
 This unique amino acid structure in the antibody is known as the idiotype,
which can be considered as a mirror of the epitope in the antigen.
 Antibodies can be raised against the idiotype by injecting the antibody into
another animal.
 This anti-idiotype antibody mimics part of the three dimensional structure of
the antigen.
 This can be used as a vaccine when the anti-idiotype antibody is injected into
a vaccinee, antibodies (antianti- idiotype antiobodies) are formed that
recognize a structure similar to part of the virus and might potentially
neutralize the virus.
Advantage:
• Antibodies against potentially significant antigen can be
produced.
Disadvantage:
• Only humoral immunity is produced.
• There is no cellular immunity and poor memory.
• Identification and preparation of idiotypes is labor intensive
and difficult.
Journals Recommended
• Vaccine,
• Journal of Antimicrobial Chemotherapy,
• Clinical Immunology and Immunopathology,
• Medical Microbiology and Immunology
Thank You

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Vaccinology lecture ppt

  • 2. • Immunization,is the process by which an individual's immune system becomes fortified against an agent (known as the immunogen). • Immunization is done through various techniques, most commonly vaccination
  • 3. Vaccinology  The science or methodology of vaccine development .  Vaccine: A vaccine is a biological preparation that improves immunity to a particular disease.  A vaccine typically contains an agent that resembles a disease- causing microorganism, and is often made from weakened or killed forms of the microbe.  The agent stimulates the body's immune system to recognize the agent as foreign, destroys it, and "remembers" it, so that the immune system can easily recognize and destroy any of these micro-organisms that it encounters later.
  • 4. Properties of an ideal vaccine  Provide long lasting immunity.  Should induce both humoral and cellular immunity.  Should not induce autoimmunity or hypersensitivity.  Should be inexpensive to produce, easy to store and administer.  Vaccines must also be perceived to be safe.  The vaccine vial may contain relevant antigen, adjuvant (usually alum), preservatives and/or traces of protein derived from the cells in which the vaccine agent was cultured e.g. egg protein.
  • 5. Types of Vaccines  Killed  Attenuated  Toxiod  Subunit  Peptide vaccines  Conjugate  DNA  Recombinant Vector Vaccines  Anti-idiotypic Vaccine
  • 6. Live Attenuated Vaccines • Live, attenuated vaccines contain a version of the living microbe that has been weakened in the lab so it can’t cause disease. • Because a live, attenuated vaccine is the closest thing to a natural infection, these vaccines are good “teachers” of the immune system: • They elicit strong cellular and antibody responses and often confer lifelong immunity with only one or two doses.
  • 7. Disadvantages • It is the nature of living things to change, or mutate, and the organisms used in live, attenuated vaccines are no different. • The remote possibility exists that an attenuated microbe in the vaccine could revert to a virulent form and cause disease. • Also, not everyone can safely receive live, attenuated vaccines. For their own protection, people who have damaged or weakened immune systems— because they have undergone chemotherapy or have HIV, for example— cannot be given live vaccines.
  • 8.  Another limitation is that live, attenuated vaccines usually need to be refrigerated to stay potent.  If the vaccine needs to be shipped overseas and stored by health care workers in developing countries that lack widespread refrigeration, a live vaccine may not be the best choice. 
  • 9. Killed Vaccines  Such vaccines are more stable and safer than live vaccines:  The dead microbes can’t mutate back to their disease-causing state.  Inactivated vaccines usually don’t require refrigeration, and they can be easily stored and transported in a freeze-dried form, which makes them accessible to people in developing countries.  Most inactivated vaccines, however, stimulate a weaker immune system response than do live vaccines.  So it is likely to take several additional doses, or booster shots, to maintain a person’s immunity.  This could be a drawback in areas where people don’t have regular access to health care and can’t get booster shots on time.
  • 10. Subunit Vaccines  Instead of the entire microbe, subunit vaccines include only the antigens that best stimulate the immune system.  In some cases, these vaccines use epitopes—the very specific parts of the antigen that antibodies or T cells recognize and bind to.  Because subunit vaccines contain only the essential antigens and not all the other molecules that make up the microbe, the chances of adverse reactions to the vaccine are lower.  Subunit vaccines can contain anywhere from 1 to 20 or more antigens.  Of course, identifying which antigens best stimulate the immune system is a tricky, time-consuming process.
  • 11. Subunit vaccines can be made in one of two ways:  The microbe can be grown in the laboratory and then chemicals are used to break it apart and gather the important antigens.  The antigen molecules can be manufactured from the microbe using recombinant DNA technology. Vaccines produced this way are called “recombinant subunit vaccines.”  A recombinant subunit vaccine has been made for hepatitis B virus. Scientists inserted hepatitis B virus genes that code for important antigens into common baker’s yeast.  The yeast then produced the antigens, which the scientists collected and purified for use in the vaccine.  HBsAg, HBxAg, etc.
  • 12. Advantages: • They can safely be given to immunosuppressed people. • They are less likely to induce side effects. Disadvantages: • Antigens may not retain their native conformation, so that antibodies produced against the subunit may not recognize the same protein on the pathogen surface. • Isolated protein does not stimulate the immune system as well as a whole organism vaccine.
  • 13. Peptide vaccines • Peptide vaccine consists of those peptides from the microbial antigen that stimulates protective immunity. • Synthetic peptides are produced by automated machines rather than by microorganisms. • Peptide immunogenicity can be increased by giving lipid micelles that transport the peptides directly into the cytoplasm of dendritic cells for presentation on Class I MHC. • Injected peptides, which are much smaller than the original virus protein, induce an IgG response. • Example: spf66 anti-malarial vaccine
  • 14. Advantages: • If the peptide that induces protective immunity is identified, it can be synthesized easily on a large scale. • It is safe and can be administered to immunodeficient and pregnant individuals. Disadvantage: • Poor antigenicity. Peptide fragments do not stimulate the immune system as whole organism vaccine. • Since peptides are closely associated with HLA alleles, some peptides may not be universally effective at inducing protective immunity.
  • 15. Toxoid Vaccines  A vaccine made from a toxin (poison) that has been made harmless but that elicits an immune response against the toxin  Based on the toxin produced by certain bacteria (e.g. tetanus or diphtheria).  These vaccines are used when a bacterial toxin is the main cause of illness.  Bacterial toxins are inactivated by treating them with formalin, a solution of formaldehyde and sterilized water.  Such “detoxified” toxins, called toxoids, are safe for use in vaccines.  When the immune system receives a vaccine containing a harmless toxoid, it learns how to fight off the natural toxin.  The immune system produces antibodies that lock onto and block the toxin.  Vaccines against diphtheria and tetanus are examples of toxoid vaccines.
  • 16. Conjugate Vaccines  A conjugate vaccine is created by covalently attaching a poor (polysaccharide organism) antigen to a carrier protein (preferably from the same micro-organism), thereby conferring the immunological attributes of the carrier on the attached antigen.  This technique for the creation of an effective immunogen is most often applied to bacterial polysaccharides for the prevention of invasive bacterial disease.  Polysaccharide coatings disguise a bacterium’s antigens so that the immature immune systems of infants and younger children can’t recognize or respond to them.
  • 17. Conjugate Vaccines-1  Conjugate vaccines are a special type of subunit vaccine to get around this problem.  When making a conjugate vaccine, scientists link antigens or toxoids from a microbe that an infant’s immune system can recognize to the polysaccharides.  The linkage helps the immature immune system to react to polysaccharide coatings and defend against the disease- causing bacterium.  The vaccine that protects against Haemophilus influenzae type B (Hib) is a conjugate vaccine and other e.g are Pneumoccocal Vaccine and Meningococcal Vaccine
  • 19.  A DNA vaccine against a microbe would evoke a strong antibody response to the free-floating antigen secreted by cells, and the vaccine also would stimulate a strong cellular response against the microbial antigens displayed on cell surfaces.  DNA vaccines can not cause the disease because they do not contain the microbe, just copies of a few of its genes.  In addition, DNA vaccines are relatively easy and inexpensive to design and produce.  Naked DNA vaccines are being tested in humans including those against the viruses that cause influenza and herpes.
  • 20. Advantages: • DNA is very stable, it resists extreme temperature and hence storage and transport are easy. • A DNA sequence can be changed easily in the laboratory. • The inserted DNA does not replicate and encodes only the proteins of interest. • There is no protein component and so there will be no immune response against the vector itself. • Because of the way the antigen is presented, there is a cell-mediated response that may be directed against any antigen in the pathogen. Disadvantages: • Potential integration of DNA into host genome leading to insertional mutagenesis. • Induction of autoimmune responses: anti-DNA antibodies may be produced against introduced DNA. • Induction of immunologic tolerance: The expression of the antigen in the host may lead to specific nonresponsiveness to that antigen.
  • 21. Recombinant Vector Vaccines • Recombinant vector vaccines are experimental vaccines similar to DNA vaccines, but they use an attenuated virus or bacterium to introduce microbial DNA to cells of the body. • “Vector” refers to the virus or bacterium used as the carrier. • In nature, viruses bind to cells and inject their genetic material into them. • In the lab, scientists take advantage of this process. • The carrier viruses then transport that microbial DNA to cells. • Recombinant vector vaccines closely mimic a natural infection and therefore do a good job of stimulating the immune system.
  • 22.  Attenuated bacteria also can be used as vectors.  In this case, the inserted genetic material causes the bacteria to display the antigens of other microbes on its surface.  In effect, the harmless bacterium mimics a harmful microbe, provoking an immune response.  Researchers are working on both bacterial and viral-based recombinant vector vaccines for HIV, rabies, and measles.
  • 23. Anti-idiotypic Vaccine  An antigen binding site in an antibody is a reflection of the three- dimensional structure of part of the antigen (epitope).  This unique amino acid structure in the antibody is known as the idiotype, which can be considered as a mirror of the epitope in the antigen.  Antibodies can be raised against the idiotype by injecting the antibody into another animal.  This anti-idiotype antibody mimics part of the three dimensional structure of the antigen.  This can be used as a vaccine when the anti-idiotype antibody is injected into a vaccinee, antibodies (antianti- idiotype antiobodies) are formed that recognize a structure similar to part of the virus and might potentially neutralize the virus.
  • 24. Advantage: • Antibodies against potentially significant antigen can be produced. Disadvantage: • Only humoral immunity is produced. • There is no cellular immunity and poor memory. • Identification and preparation of idiotypes is labor intensive and difficult.
  • 25. Journals Recommended • Vaccine, • Journal of Antimicrobial Chemotherapy, • Clinical Immunology and Immunopathology, • Medical Microbiology and Immunology