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Vaccines
Contents
 Vaccines
 Vaccination
 Properties of an ideal vaccine
 Mechanism of a vaccine
 Types of vaccine
 Methods for production of vaccine
 National immunization Shedule
 Common side effect of any vaccine
 Risk associated with vaccines
 References
What are Vaccines?
 A vaccine is a biological
preparation that improves
immunity to a particular
disease
 Name derived from Latin word
“vacca” which means “cow”
 It contains certain agent that
only resembles a disease
causing microorganism but it
also stimulates body’s immune
system to recognize foreign
agents to destroy it and keep
record of it.
Vaccination
 The science or methodology of vaccine development
 Vaccination is the administration of antigenic material (vaccine) to stimulate an
individual’s immune system to develop adaptive immunity to a pathogen.
 Most vaccines are given by an injection, but some are given orally (by mouth) or
sprayed into the nose.
 Vaccine can prevent from a infection
Properties of an ideal vaccine
• Single dose
• Should produce long lasting immunity
• Should not induce hypersensitivity
• Should be inexpensive to produce, easy to store and
administer
• Vaccines must also be perceived to be safe
• Effective in all subjects (old and very young)
• Is stable under various conditions (temperature, light)
• Is available in unlimited quantities
Mechanism of a vaccine
When you get a vaccine, your immune system responds. It:
 Recognizes the invading germ, such as the virus or bacteria.
 Produces antibodies, Antibodies are proteins produced naturally
by the immune system to fight disease.
 Develop memory: Remembers the disease and how to fight it. If
you are then exposed to the germ in the future, your immune
system can quickly destroy it before you become unwell.
Once exposed to one or more doses of a vaccine, we typically remain
protected against a disease for years, decades or even a lifetime. This
is what makes vaccines so effective.
Types of vaccines
Killed
Attenuated
Toxoids
Subunit
Peptide vaccine
Conjugate
DNA vaccine
Recombinant Vector
Vaccines
Killed/ inactivated Vaccine
 Scientist produce inactivated vaccines by killing the disease-causing
microbe with chemicals, heat, or radiation.
 Such vaccines are more stable and safer than live vaccines
 Because dead microbes cannot mutate back to their disease causing
state
 Inactivated vaccine usually do not require refrigeration, usually they
can be easily stored and transported in a freeze-dried form, which
makes them accessible to people in developing countries
 Chemical inactivation with formaldehyde or various alkylating agent
has been successful
 The Salk polio vaccine is produced by formaldehyde inactivation of
Polio virus
 Most inactivated vaccines, however, stimulate a weaker immune system
response than do live vaccines
 Killed vaccine often required repeated boosters to achieve a protective
immune status as they do not replicate in host
 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
 Example: Vaccines against Influenza, Polio, Hepatitis A, Typhoid ,Cholera ,
Pertussis and rabies.
Attenuated/ live vaccine
 Microorganisms can be attenuated or disabled so that they lose their
ability to cause significant disease but retain their capacity for transient
growth within an inoculated host
 Attenuation can often be achieved by growing a pathogenic bacterium
or virus for prolonged periods under abnormal culture conditions
 For example, an attenuated strain of Mycobacterium bovis called Bacillus
Calmette- Guerin (BCG) was developed by growing M. bovis on a
medium containing increasing concentrations of bile.
 Elicit strong cellular and antibody responses
 Confer lifelong immunity with only one or two doses
 Example: BCG - Typhoid oral - bacterial Oral polio , Yellow fever , Measles ,
, Rubella , Mumps , Chicken pox
Disadvantages:
 Pathogens could revert to a virulent form and cause disease
 Need to be refrigerated to stay potent
 Also, not everyone can safely receive live, attenuated vaccines.
Toxoids vaccines
 A vaccine made from a toxin (poison) that has been made harmless but that elicits an
immune response against the toxin
 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.
 When the immune system receives a vaccine containing a harmless toxoid, it learns
how to fight off the natural toxin.
 Example: Tetanus, Diphtheria bacterial vaccines
Subunit Vaccines
 Instead of the entire microbe, 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
 The chances of adverse reactions to the vaccine are lower
 They can safely be given to immunosuppressed people
 They are less likely to induce side effects
 Example: Gardasil, Influenza, Hepatitis B
Disadvantages:
 Of course, identifying which antigens best stimulate the immune system is a tricky,
time-consuming process.
Peptide Vaccines
 A peptide vaccine consist of synthetic peptides that are able to induce
protective immune response when administrated into host
 To produce peptide vaccine it is necessary to identify immunogenic
regions also known as epitopes on the antigenic protein
 Epitopes binds to antibodies produced by specific B cells and recognized
by receptors on the surface of activated T cells
 Example: spf66 anti-malarial vaccine, Tetanus vaccine
Why Synthetic Peptide Vaccines?
 Chemically well defined, selective and safe
 Stable at ambient temperature
 Cost effective
Drawback of Peptide Vaccines
 Poor antigenicity
Peptide fragments do not stimulate the immune system as whole
organism vaccine.
Conjugate Vaccine
 A conjugate vaccine combines a weak antigen with a
strong antigen as a carrier so that the immune system
has a stronger response to the weak antigen.
 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
 The linkage helps the immature immune system to
react to polysaccharide coatings and defend against
the disease causing bacterium
 Example : Pneumococcal, meningococcal, Haemophilus
influenza type B vaccine
DNA vaccine
 A DNA vaccine against a microbe would evoke a strong antibody response to the free-
floating antigen secreted by cells
 The vaccine also would stimulate a strong cellular response against the microbial
antigens displayed on cell surfaces
Why DNA vaccine?
 Uses only the DNA from infectious organisms
 Provide both humoral and cell mediated immunity
 Refrigeration is not required
 Relatively easy and inexpensive
 Example: influenza virus, hepatitis B virus, human immunodeficiency virus, rabies virus
etc
Recombinant Vector Vaccine
 Experimental vaccines similar to DNA vaccines, but they use an
attenuated virus or bacterium to introduce microbial DNA to cells of the
body
 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
 Attenuated bacteria also can be used as vectors
 Example: in yellow fever vaccine, a number of organisms have been used
used as the vector in such preparations such as
 vaccinia virus
 canarypox virus
 attenuated poliovirus
 adenoviruses
 attenuated strains of Salmonella
 BCG strain of Mycobacterium bovis and certain strains of Streptococcus
that normally exist in the oral cavity.
General method for vaccine production
Step 5: Packaging
Step 4: Addition of other components
Step 3: Purification
Step 2: Isolation of the antigen
Step 1: Generation of the antigen
Step-wise process
Generation of antigen
In order to generate the antigen, pathogen’s proteins or DNA need to be grown and
harvested using following mechanisms
 Viruses are grown on primary cell such as cell from chicken embryo or using fertilized
egg that reproduce repeatedly
 Bacteria are grown in bioreactor which are devices that use a particular growth medium
that optimizes the production of the antigen
Release and isolation
 The aim of the second step is to release as much virus or bacteria as
possible
 To achieve this the antigen will be separated from the cell and isolated
from the proteins and other parts of the growth medium that are still
present
Purification
 In the third step the antigen will need to be purified in order to produce a high
purity and quality product
 This will be accomplished using different technique for protein purification and
several separation steps will be carried out
 For weakened or attenuated viruses no further purification may be required
 Recombinant proteins need many operations involving ultrafiltration and column
chromatography for purification before they are ready for administration
Addition of other components
 The fourth step includes the addition of an adjuvant , stabilizers
and preservatives
 The role of the adjuvant (aluminum salt) is to enhance the
immune response of the antigen , the stabilizers (MgCl2 for OPV,
MgSO4 for measles, gelatin) increase the storage life and
preservatives (Formaldehyde, or Phenol derivatives) allow the
use of multi dose vials and prevent bacterial and fungal growth
 It is difficult to develop and produce combination vaccines due
to the possibility of incompatibilities and interactions among the
antigens and other ingredients of the vaccines.
Packaging
 Once the vaccine is put in recipient vessel it needs to be protected from air, water
and human contamination
 The environment needs to be protected from spillage of the antigens
 For the packing and shipping vaccine must be stored in 2 0 to 8 0 C
 Temperatures tracking device is included in each shipment
 And finally the vaccines are labelled and distributed worldwide
Common side effect of any vaccine can
include
 Injection site reactions (pain, swelling and redness)
 Mild fever
 Shivering
 Fatigue
 Headache
 Muscle and joint pain
Risk associated with vaccines
 Vaccines also have some sort of risks, like:
 The primary risk associated with vaccines, especially vaccines that utilize
live organisms, is that the vaccine itself causes illness
 Vaccine may behave as a super antigen and over stimulate the immune
system
 Some individuals may have an allergic reaction to the vaccine, especially
vaccines produced in Embryonated chicken eggs and in transgenic
plants.
National Immunization Shedule
 The first visit when infant is 6 weeks old
 2 &3rd visits - at intervals of 1 to 2 months
 Oral polio vaccine may be given concurrently with DPT
References
 Janes Kuby, 2007, Vaccines, Immunology, W.H. Freeman and Company, Newyork,
sixth Edition, Pg. 413- 428
 Satyanarayana U., 2010, Vaccines, Biotechnology, BOOK’S AND ALLIED (P) Ltd,
Kolkata, sixth edition, Pg. 211-212.
 Kuby Immunology, Seventh Edition
 World Health Organization http://www.who.int/topics/vaccines/en/
 A federal government Website managed by the U.S. Department of Health and
Human Services http://www.vaccines.gov/more_info/types/
 www.ncbi.nlm.nih.gov/pmc/articles/PMC18103
 http://www.niaid.nih.gov/topics/hivaids/research/vaccines /Pages/default.aspx
 http://www.ncbi.nlm.nih.gov/pubmed/19208455
 http://www.biotec.or.th/biosafety/download/biotec%20seminar%202.pdf
 http://www.cfsciences.com/pdf?3.%20vaccine%20production%20ver7.pdf
 www.hsc.gov.sg
 www.sonofi.com
 www.sciencedirect.com
 www.shareyourarticles.com
 Life sciences: Fundamental and practice
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Vaccines

  • 2. Contents  Vaccines  Vaccination  Properties of an ideal vaccine  Mechanism of a vaccine  Types of vaccine  Methods for production of vaccine  National immunization Shedule  Common side effect of any vaccine  Risk associated with vaccines  References
  • 3. What are Vaccines?  A vaccine is a biological preparation that improves immunity to a particular disease  Name derived from Latin word “vacca” which means “cow”  It contains certain agent that only resembles a disease causing microorganism but it also stimulates body’s immune system to recognize foreign agents to destroy it and keep record of it.
  • 4. Vaccination  The science or methodology of vaccine development  Vaccination is the administration of antigenic material (vaccine) to stimulate an individual’s immune system to develop adaptive immunity to a pathogen.  Most vaccines are given by an injection, but some are given orally (by mouth) or sprayed into the nose.  Vaccine can prevent from a infection
  • 5. Properties of an ideal vaccine • Single dose • Should produce long lasting immunity • Should not induce hypersensitivity • Should be inexpensive to produce, easy to store and administer • Vaccines must also be perceived to be safe • Effective in all subjects (old and very young) • Is stable under various conditions (temperature, light) • Is available in unlimited quantities
  • 6. Mechanism of a vaccine When you get a vaccine, your immune system responds. It:  Recognizes the invading germ, such as the virus or bacteria.  Produces antibodies, Antibodies are proteins produced naturally by the immune system to fight disease.  Develop memory: Remembers the disease and how to fight it. If you are then exposed to the germ in the future, your immune system can quickly destroy it before you become unwell. Once exposed to one or more doses of a vaccine, we typically remain protected against a disease for years, decades or even a lifetime. This is what makes vaccines so effective.
  • 7.
  • 8. Types of vaccines Killed Attenuated Toxoids Subunit Peptide vaccine Conjugate DNA vaccine Recombinant Vector Vaccines
  • 9. Killed/ inactivated Vaccine  Scientist produce inactivated vaccines by killing the disease-causing microbe with chemicals, heat, or radiation.  Such vaccines are more stable and safer than live vaccines  Because dead microbes cannot mutate back to their disease causing state  Inactivated vaccine usually do not require refrigeration, usually they can be easily stored and transported in a freeze-dried form, which makes them accessible to people in developing countries  Chemical inactivation with formaldehyde or various alkylating agent has been successful  The Salk polio vaccine is produced by formaldehyde inactivation of Polio virus
  • 10.  Most inactivated vaccines, however, stimulate a weaker immune system response than do live vaccines  Killed vaccine often required repeated boosters to achieve a protective immune status as they do not replicate in host  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  Example: Vaccines against Influenza, Polio, Hepatitis A, Typhoid ,Cholera , Pertussis and rabies.
  • 11. Attenuated/ live vaccine  Microorganisms can be attenuated or disabled so that they lose their ability to cause significant disease but retain their capacity for transient growth within an inoculated host  Attenuation can often be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions  For example, an attenuated strain of Mycobacterium bovis called Bacillus Calmette- Guerin (BCG) was developed by growing M. bovis on a medium containing increasing concentrations of bile.
  • 12.  Elicit strong cellular and antibody responses  Confer lifelong immunity with only one or two doses  Example: BCG - Typhoid oral - bacterial Oral polio , Yellow fever , Measles , , Rubella , Mumps , Chicken pox Disadvantages:  Pathogens could revert to a virulent form and cause disease  Need to be refrigerated to stay potent  Also, not everyone can safely receive live, attenuated vaccines.
  • 13. Toxoids vaccines  A vaccine made from a toxin (poison) that has been made harmless but that elicits an immune response against the toxin  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.  When the immune system receives a vaccine containing a harmless toxoid, it learns how to fight off the natural toxin.  Example: Tetanus, Diphtheria bacterial vaccines
  • 14. Subunit Vaccines  Instead of the entire microbe, 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  The chances of adverse reactions to the vaccine are lower  They can safely be given to immunosuppressed people  They are less likely to induce side effects  Example: Gardasil, Influenza, Hepatitis B Disadvantages:  Of course, identifying which antigens best stimulate the immune system is a tricky, time-consuming process.
  • 15. Peptide Vaccines  A peptide vaccine consist of synthetic peptides that are able to induce protective immune response when administrated into host  To produce peptide vaccine it is necessary to identify immunogenic regions also known as epitopes on the antigenic protein  Epitopes binds to antibodies produced by specific B cells and recognized by receptors on the surface of activated T cells  Example: spf66 anti-malarial vaccine, Tetanus vaccine
  • 16. Why Synthetic Peptide Vaccines?  Chemically well defined, selective and safe  Stable at ambient temperature  Cost effective Drawback of Peptide Vaccines  Poor antigenicity Peptide fragments do not stimulate the immune system as whole organism vaccine.
  • 17. Conjugate Vaccine  A conjugate vaccine combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.  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  The linkage helps the immature immune system to react to polysaccharide coatings and defend against the disease causing bacterium  Example : Pneumococcal, meningococcal, Haemophilus influenza type B vaccine
  • 18. DNA vaccine  A DNA vaccine against a microbe would evoke a strong antibody response to the free- floating antigen secreted by cells  The vaccine also would stimulate a strong cellular response against the microbial antigens displayed on cell surfaces Why DNA vaccine?  Uses only the DNA from infectious organisms  Provide both humoral and cell mediated immunity  Refrigeration is not required  Relatively easy and inexpensive  Example: influenza virus, hepatitis B virus, human immunodeficiency virus, rabies virus etc
  • 19.
  • 20. Recombinant Vector Vaccine  Experimental vaccines similar to DNA vaccines, but they use an attenuated virus or bacterium to introduce microbial DNA to cells of the body  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
  • 21.  Attenuated bacteria also can be used as vectors  Example: in yellow fever vaccine, a number of organisms have been used used as the vector in such preparations such as  vaccinia virus  canarypox virus  attenuated poliovirus  adenoviruses  attenuated strains of Salmonella  BCG strain of Mycobacterium bovis and certain strains of Streptococcus that normally exist in the oral cavity.
  • 22. General method for vaccine production Step 5: Packaging Step 4: Addition of other components Step 3: Purification Step 2: Isolation of the antigen Step 1: Generation of the antigen Step-wise process
  • 23. Generation of antigen In order to generate the antigen, pathogen’s proteins or DNA need to be grown and harvested using following mechanisms  Viruses are grown on primary cell such as cell from chicken embryo or using fertilized egg that reproduce repeatedly  Bacteria are grown in bioreactor which are devices that use a particular growth medium that optimizes the production of the antigen
  • 24. Release and isolation  The aim of the second step is to release as much virus or bacteria as possible  To achieve this the antigen will be separated from the cell and isolated from the proteins and other parts of the growth medium that are still present
  • 25. Purification  In the third step the antigen will need to be purified in order to produce a high purity and quality product  This will be accomplished using different technique for protein purification and several separation steps will be carried out  For weakened or attenuated viruses no further purification may be required  Recombinant proteins need many operations involving ultrafiltration and column chromatography for purification before they are ready for administration
  • 26. Addition of other components  The fourth step includes the addition of an adjuvant , stabilizers and preservatives  The role of the adjuvant (aluminum salt) is to enhance the immune response of the antigen , the stabilizers (MgCl2 for OPV, MgSO4 for measles, gelatin) increase the storage life and preservatives (Formaldehyde, or Phenol derivatives) allow the use of multi dose vials and prevent bacterial and fungal growth  It is difficult to develop and produce combination vaccines due to the possibility of incompatibilities and interactions among the antigens and other ingredients of the vaccines.
  • 27. Packaging  Once the vaccine is put in recipient vessel it needs to be protected from air, water and human contamination  The environment needs to be protected from spillage of the antigens  For the packing and shipping vaccine must be stored in 2 0 to 8 0 C  Temperatures tracking device is included in each shipment  And finally the vaccines are labelled and distributed worldwide
  • 28. Common side effect of any vaccine can include  Injection site reactions (pain, swelling and redness)  Mild fever  Shivering  Fatigue  Headache  Muscle and joint pain
  • 29. Risk associated with vaccines  Vaccines also have some sort of risks, like:  The primary risk associated with vaccines, especially vaccines that utilize live organisms, is that the vaccine itself causes illness  Vaccine may behave as a super antigen and over stimulate the immune system  Some individuals may have an allergic reaction to the vaccine, especially vaccines produced in Embryonated chicken eggs and in transgenic plants.
  • 30. National Immunization Shedule  The first visit when infant is 6 weeks old  2 &3rd visits - at intervals of 1 to 2 months  Oral polio vaccine may be given concurrently with DPT
  • 31. References  Janes Kuby, 2007, Vaccines, Immunology, W.H. Freeman and Company, Newyork, sixth Edition, Pg. 413- 428  Satyanarayana U., 2010, Vaccines, Biotechnology, BOOK’S AND ALLIED (P) Ltd, Kolkata, sixth edition, Pg. 211-212.  Kuby Immunology, Seventh Edition  World Health Organization http://www.who.int/topics/vaccines/en/  A federal government Website managed by the U.S. Department of Health and Human Services http://www.vaccines.gov/more_info/types/  www.ncbi.nlm.nih.gov/pmc/articles/PMC18103  http://www.niaid.nih.gov/topics/hivaids/research/vaccines /Pages/default.aspx  http://www.ncbi.nlm.nih.gov/pubmed/19208455
  • 32.  http://www.biotec.or.th/biosafety/download/biotec%20seminar%202.pdf  http://www.cfsciences.com/pdf?3.%20vaccine%20production%20ver7.pdf  www.hsc.gov.sg  www.sonofi.com  www.sciencedirect.com  www.shareyourarticles.com  Life sciences: Fundamental and practice