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Conventional and Genomic
Vaccines Products
WhatVaccines do:WhatVaccines do:
Increase Resistance to InfectionIncrease Resistance to Infection
There are many ways to improveThere are many ways to improve
general health:general health:
1. Proper nutrition,1. Proper nutrition,
2. Exercise,2. Exercise,
3. Healthy lifestyle,3. Healthy lifestyle,
and…and…
4. Vaccination
WhyVaccination?
Vaccines control diseases and
can protect individual animals
from illness and death.
 A vaccine is a biological preparation that
provides active acquired immunity to a
particular disease.
 A vaccine typically contains an agent that
is similar to a disease-causing
microorganism.
 It is often made from weakened or killed
forms of the microbe (its toxins or one of
its surface proteins).
 It stimulates the body's immune
system to recognize the agent in the
form of risk, destroy it, and keep a
record of it, so that the immune
system can more easily recognize
and destroy any of these
microorganisms that it later
encounters.
 Vaccines can be prophylactic (example: to
prevent the effects of a future infection by any
natural pathogen OR therapeutic (example:
vaccines against cancer are also being
investigated).
 Immunization or Vaccination: A procedure
designed to increase concentrations of
antibodies and/or effector T-cells which are
reactive against infection (or cancer).
DifferentTypes ofVaccines
1. WeakenedVaccine
(Modified Live)
2. Inactivated (Killed)Vaccine
3. ToxoidVaccine
4. SubunitVaccine
Weakened (Modified Live)
Vaccines
Produced by weakening a live microorganism or
removing it’s disease-causing ability.
Advantages Disadvantages
- They produce a large
immune response
- Have to receive the
vaccine once or twice.
- They have to be kept in
special conditions, like
refrigeration.
- They can mutate and
might cause the disease.
Inactivated (killed)Vaccines
These vaccines are produced
by killing the infectious agent.
Advantages Disadvantages
- They do not have to
be refrigerated.
- They will never come
back to life and cause
the disease.
- They usually require
booster shots because
they only weakly
stimulate the immune
system to make
antibodies.
Limitations To Traditional Vaccines:
1. Can not grow all organisms in
culture
2. Expense
3. Insufficient attenuation
4. Reversion to infectious state
5. Need refrigeration
6. Do not work for all infectious
agents
7. Immature immunity for
infants/children.
New Generation of Vaccines:
• Recombinant DNA technology is being used to
produce a new generation of vaccines.
Virulence genes are deleted and organism is still
able to stimulate an immune response.
Live nonpathogenic strains can carry antigenic
determinants from pathogenic strains.
If the agent cannot be maintained in culture, genes
of proteins for antigenic determinants can be cloned
and expressed in an alternative host e.g. E. coli.
INTRODUCTIONINTRODUCTION
DNA vaccine is DNA sequence used as a
vaccine.
This DNA Sequence code for antigenic
protein of pathogen.
As this DNA inserted into cells it is
translated to form antigenic protein. As
this protein is foreign to cells, so
immune response raised against this
protein.
In this way, DNA vaccine provide
immunity against that pathogen.
DNA vaccinesVsTraditional vaccinesDNA vaccinesVsTraditional vaccines
DNA vaccines Traditional vaccines
 Uses only the DNA from
infectious organisms.
 Avoid the risk of using
actual infectious
organism.
 Provide both Humoral &
Cell mediated immunity
 Refrigeration is not
required
 Uses weakened or killed
form of infectious
organism.
 Create possible risk of
the vaccine being fatal.
 Provide primarily
Humoral immunity
 Usually requires
Refrigeration.
HOW DNAVACCINE IS MADE
Viral gene
Expression
plasmid
Plasmid with foreign gene
Recombinant DNA
Technology
Bacterial
cell
Transform into bacterial cell
Plasmi
d DNA
Plasmid DNA get Amplified
Plasmid DNA
Purified
Ready to use
ADVANTAGES
1. Produce both Humoral & cell mediated
immunity
2. Focused on Antigen of interest
2. Long term immunity
3. Refrigeration is not required
4. Stable for storage
DISADVANTAGES
1. Limited to protein immunogen only
2. Extended immuno stimulation leads to chronic
inflammation
3. Some antigen require processing which
sometime does not occur.
Vaccine preventable diseases
Diphtheria Tetanus Whooping cough
Meningitis Hib, Strep, Neisseria
Measels
Polio
Principles ofVaccination
•Protection from infectious disease.
•Usually indicated by the presence of
antibody.
•Very specific to a single organism.
Types ofVaccination
• Active:
Protection produced by the person's own immune
system, longer time and may be long lasting.
• Natural : eg – Infection
• Artificial : eg –Vaccination
• Passive: Protection transferred from another person
or animal,Temporary wanes out by time.
• Natural,
Examples: IgG crossing placenta to protect fetus
Antibodies acquired by baby through breast milk.
• Artificial
Examples:Treatment with antiserum, antitoxin.
Monoclonal antibody
• Derived from a single type, or clone, of
antibody-producing cells (B cells)
• Antibody is specific to a single antigen or
closely related group of antigens
• Used for diagnosis and therapy of certain
cancers and autoimmune and infectious
diseases
Types of Active vaccines
•Living attenuated; virus or
bacteria
•Killed or Inactivated; Whole
(Virus or Bacteria).
•Fractionated
•protein-based ( e.g. toxoid )
•polysaccharide-based
1. Live attenuatedVaccines
• Attenuated (weakened) form of the "wild" virus or
bacterium
• Must replicate to be effective
• Immune response similar to natural infection
• Usually produce immunity with one dose, except those
administered orally
• Severe reactions possible
• Interference from circulating antibody
• Fragile – must be stored and handled carefully
• Viral:
• measles, mumps,rubella, varicella/zoster, yellow fever, rotavirus
etc..
• Bacterial BCG, oral typhoid
2. InactivatedVaccines
• Cannot replicate
• Generally not as effective as live vaccines
• Less interference from circulating antibody than live vaccines
• Generally require 3-5 doses
• Immune response mostly humoral
• Antibody titre may diminish with time
• Whole cell vaccine
• Viral polio, hepatitis A, rabies, influenza
• Bacterial: pertussis, typhoid, cholera, plague
• Fractionated
• Subunit hepatitis B, influenza, acellular pertussis,human
papillomavirus, anthrax
• Toxoid: diphtheria, tetanus
Pure PolysaccharideVaccines
• Not consistently immunogenic in children younger than 2
years of age
• No booster response
• Antibody with less functional activity
• Immunogenicity improved by conjugation
Polysaccharide Vaccines
• Pure polysaccharide
• pneumococcal
• meningococcal
• SalmonellaTyphi (Vi
• Conjugate polysaccharide
•Haemophilus influenzae type b
•pneumococcal
•meningococcal
DNA vaccine
• Is a coding DNA sequence used as a vaccine when injected
into cells, it is translated to form antigenic protein of
pathogens. As this protein is foreign to cells , so immune
response raised against this protein.
• Advantages over traditional vaccines:
• Uses only the DNA from infectious organisms.
• Avoid the risk of using actual infectious organism.
• Provide both Humoral & Cell mediated immunity
• Refrigeration is not required
• Expressed inside cell, so no problem with all kinetics
• Disadvantages:
 Limited to protein immunogen only
 Extended immunostimulation leads to chronic inflammation
 Some antigen require processing which sometime does not occur
Nucleic Acid (DNA)Vaccination
• Nucleic acid (DNA) vaccination is a technique for
stimulation of the immune response against a disease
causing agent by injecting the genetically engineered
DNA of it to create protection .
• This technique is still under investigation, and it has been
applied to a number of viral, bacterial and parasitic
models of disease, as well as to several tumour models.
• Although DNA vaccines are untested in the clinical
setting, they have a number of potential advantages over
conventional vaccines, including the ability to induce a
wider range of immune response types and no risk for
infection
DNA vaccine technology
Viral/bacterial
gene
Expression
plasmid
Plasmid carrying foreign gene Inject into host in different
delivery ways:
Recombinant DNA
Technology
Delivery of DNA vaccines
•Syringe delivery
Either intramuscularly or
Intradermally
Gene gun delivery:-
 Plasmid DNA into gold particles
 Infected into body with gene gun.
Muscle Cells Plasmid DNA
+
What happens after you inject into muscle?
DNA vaccine works by two pathways:
endogenous pathway and exogenous pathway
mRNA
Antigenic
Protein
MHC-I
Plasmid
DNA
Nucleus
1. endogenous pathway: antigenic protein stays
inside cell
Multiply
Memory T cells
T- Helper Cell
2. Exogenous pathway: immunogenic protein
exported outside cells
Antigenic Protein comes
outside
Phagocytosed
Antigen Presenting Cell
Antigenic Peptides
T- Helper Cell
Cytokines
Activated B-Cell Memory B-Cell
Plasma B-Cell
Memory
Antibodies
MHC-II
When the virus enters body second time
Viral Protein
Memory T-Cell
Antibodies
Current DNA vaccine clinical trials.
Ferraro B et al. Clin Infect
Dis. 2011;53:296-302
Toxoids
 Toxoids made by inactivating the toxin that
some infectious agents create.
 Toxoids used against Tetanus and Diphtheria.
Advantages Disadvantages
- You only have to have
the vaccine once or
twice.
- They will never be
reactivated and cause
the disease.
- They have to be
refrigerated.
Subunit Vaccines
 Made by taking apart an infectious agent and only
using the antigenic part (the part that stimulates
an immune response).
 Example vaccines: Hepatitis B and Streptococcus
pneumoniae
Advantages Disadvantages
- They cannot cause
the disease.
- They are more difficult to
make and require new,
expensive technology.
Conventional and genomic vaccines

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Conventional and genomic vaccines

  • 2. WhatVaccines do:WhatVaccines do: Increase Resistance to InfectionIncrease Resistance to Infection There are many ways to improveThere are many ways to improve general health:general health: 1. Proper nutrition,1. Proper nutrition, 2. Exercise,2. Exercise, 3. Healthy lifestyle,3. Healthy lifestyle, and…and… 4. Vaccination
  • 3. WhyVaccination? Vaccines control diseases and can protect individual animals from illness and death.
  • 4.  A vaccine is a biological preparation that provides active acquired immunity to a particular disease.  A vaccine typically contains an agent that is similar to a disease-causing microorganism.  It is often made from weakened or killed forms of the microbe (its toxins or one of its surface proteins).
  • 5.  It stimulates the body's immune system to recognize the agent in the form of risk, destroy it, and keep a record of it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.
  • 6.  Vaccines can be prophylactic (example: to prevent the effects of a future infection by any natural pathogen OR therapeutic (example: vaccines against cancer are also being investigated).  Immunization or Vaccination: A procedure designed to increase concentrations of antibodies and/or effector T-cells which are reactive against infection (or cancer).
  • 7. DifferentTypes ofVaccines 1. WeakenedVaccine (Modified Live) 2. Inactivated (Killed)Vaccine 3. ToxoidVaccine 4. SubunitVaccine
  • 8. Weakened (Modified Live) Vaccines Produced by weakening a live microorganism or removing it’s disease-causing ability. Advantages Disadvantages - They produce a large immune response - Have to receive the vaccine once or twice. - They have to be kept in special conditions, like refrigeration. - They can mutate and might cause the disease.
  • 9. Inactivated (killed)Vaccines These vaccines are produced by killing the infectious agent. Advantages Disadvantages - They do not have to be refrigerated. - They will never come back to life and cause the disease. - They usually require booster shots because they only weakly stimulate the immune system to make antibodies.
  • 10. Limitations To Traditional Vaccines: 1. Can not grow all organisms in culture 2. Expense 3. Insufficient attenuation 4. Reversion to infectious state 5. Need refrigeration 6. Do not work for all infectious agents 7. Immature immunity for infants/children.
  • 11. New Generation of Vaccines: • Recombinant DNA technology is being used to produce a new generation of vaccines. Virulence genes are deleted and organism is still able to stimulate an immune response. Live nonpathogenic strains can carry antigenic determinants from pathogenic strains. If the agent cannot be maintained in culture, genes of proteins for antigenic determinants can be cloned and expressed in an alternative host e.g. E. coli.
  • 12.
  • 13. INTRODUCTIONINTRODUCTION DNA vaccine is DNA sequence used as a vaccine. This DNA Sequence code for antigenic protein of pathogen. As this DNA inserted into cells it is translated to form antigenic protein. As this protein is foreign to cells, so immune response raised against this protein. In this way, DNA vaccine provide immunity against that pathogen.
  • 14. DNA vaccinesVsTraditional vaccinesDNA vaccinesVsTraditional vaccines DNA vaccines Traditional vaccines  Uses only the DNA from infectious organisms.  Avoid the risk of using actual infectious organism.  Provide both Humoral & Cell mediated immunity  Refrigeration is not required  Uses weakened or killed form of infectious organism.  Create possible risk of the vaccine being fatal.  Provide primarily Humoral immunity  Usually requires Refrigeration.
  • 15. HOW DNAVACCINE IS MADE Viral gene Expression plasmid Plasmid with foreign gene Recombinant DNA Technology
  • 17. Plasmid DNA get Amplified
  • 19. ADVANTAGES 1. Produce both Humoral & cell mediated immunity 2. Focused on Antigen of interest 2. Long term immunity 3. Refrigeration is not required 4. Stable for storage
  • 20. DISADVANTAGES 1. Limited to protein immunogen only 2. Extended immuno stimulation leads to chronic inflammation 3. Some antigen require processing which sometime does not occur.
  • 21. Vaccine preventable diseases Diphtheria Tetanus Whooping cough Meningitis Hib, Strep, Neisseria Measels Polio
  • 22. Principles ofVaccination •Protection from infectious disease. •Usually indicated by the presence of antibody. •Very specific to a single organism.
  • 23. Types ofVaccination • Active: Protection produced by the person's own immune system, longer time and may be long lasting. • Natural : eg – Infection • Artificial : eg –Vaccination • Passive: Protection transferred from another person or animal,Temporary wanes out by time. • Natural, Examples: IgG crossing placenta to protect fetus Antibodies acquired by baby through breast milk. • Artificial Examples:Treatment with antiserum, antitoxin.
  • 24. Monoclonal antibody • Derived from a single type, or clone, of antibody-producing cells (B cells) • Antibody is specific to a single antigen or closely related group of antigens • Used for diagnosis and therapy of certain cancers and autoimmune and infectious diseases
  • 25. Types of Active vaccines •Living attenuated; virus or bacteria •Killed or Inactivated; Whole (Virus or Bacteria). •Fractionated •protein-based ( e.g. toxoid ) •polysaccharide-based
  • 26. 1. Live attenuatedVaccines • Attenuated (weakened) form of the "wild" virus or bacterium • Must replicate to be effective • Immune response similar to natural infection • Usually produce immunity with one dose, except those administered orally • Severe reactions possible • Interference from circulating antibody • Fragile – must be stored and handled carefully • Viral: • measles, mumps,rubella, varicella/zoster, yellow fever, rotavirus etc.. • Bacterial BCG, oral typhoid
  • 27. 2. InactivatedVaccines • Cannot replicate • Generally not as effective as live vaccines • Less interference from circulating antibody than live vaccines • Generally require 3-5 doses • Immune response mostly humoral • Antibody titre may diminish with time • Whole cell vaccine • Viral polio, hepatitis A, rabies, influenza • Bacterial: pertussis, typhoid, cholera, plague • Fractionated • Subunit hepatitis B, influenza, acellular pertussis,human papillomavirus, anthrax • Toxoid: diphtheria, tetanus
  • 28. Pure PolysaccharideVaccines • Not consistently immunogenic in children younger than 2 years of age • No booster response • Antibody with less functional activity • Immunogenicity improved by conjugation
  • 29. Polysaccharide Vaccines • Pure polysaccharide • pneumococcal • meningococcal • SalmonellaTyphi (Vi • Conjugate polysaccharide •Haemophilus influenzae type b •pneumococcal •meningococcal
  • 30. DNA vaccine • Is a coding DNA sequence used as a vaccine when injected into cells, it is translated to form antigenic protein of pathogens. As this protein is foreign to cells , so immune response raised against this protein. • Advantages over traditional vaccines: • Uses only the DNA from infectious organisms. • Avoid the risk of using actual infectious organism. • Provide both Humoral & Cell mediated immunity • Refrigeration is not required • Expressed inside cell, so no problem with all kinetics • Disadvantages:  Limited to protein immunogen only  Extended immunostimulation leads to chronic inflammation  Some antigen require processing which sometime does not occur
  • 31. Nucleic Acid (DNA)Vaccination • Nucleic acid (DNA) vaccination is a technique for stimulation of the immune response against a disease causing agent by injecting the genetically engineered DNA of it to create protection . • This technique is still under investigation, and it has been applied to a number of viral, bacterial and parasitic models of disease, as well as to several tumour models. • Although DNA vaccines are untested in the clinical setting, they have a number of potential advantages over conventional vaccines, including the ability to induce a wider range of immune response types and no risk for infection
  • 32. DNA vaccine technology Viral/bacterial gene Expression plasmid Plasmid carrying foreign gene Inject into host in different delivery ways: Recombinant DNA Technology
  • 33. Delivery of DNA vaccines •Syringe delivery Either intramuscularly or Intradermally
  • 34. Gene gun delivery:-  Plasmid DNA into gold particles  Infected into body with gene gun.
  • 35. Muscle Cells Plasmid DNA + What happens after you inject into muscle? DNA vaccine works by two pathways: endogenous pathway and exogenous pathway
  • 38. 2. Exogenous pathway: immunogenic protein exported outside cells Antigenic Protein comes outside
  • 39. Phagocytosed Antigen Presenting Cell Antigenic Peptides T- Helper Cell Cytokines Activated B-Cell Memory B-Cell Plasma B-Cell Memory Antibodies MHC-II
  • 40. When the virus enters body second time Viral Protein Memory T-Cell Antibodies
  • 41. Current DNA vaccine clinical trials. Ferraro B et al. Clin Infect Dis. 2011;53:296-302
  • 42. Toxoids  Toxoids made by inactivating the toxin that some infectious agents create.  Toxoids used against Tetanus and Diphtheria. Advantages Disadvantages - You only have to have the vaccine once or twice. - They will never be reactivated and cause the disease. - They have to be refrigerated.
  • 43. Subunit Vaccines  Made by taking apart an infectious agent and only using the antigenic part (the part that stimulates an immune response).  Example vaccines: Hepatitis B and Streptococcus pneumoniae Advantages Disadvantages - They cannot cause the disease. - They are more difficult to make and require new, expensive technology.

Editor's Notes

  1. For more information, see the Bodily Defenses module in the Organ Systems Web curriculum at peer.tamu.edu
  2. Knowledge
  3. Knowledge
  4. Current DNA vaccine clinical trials. At the time of publication, 43 clinical trials evaluating DNA vaccines were listed as on-going in the clinicaltrials.gov database. The large pie chart shows the percentage of trials by vaccine target. The inset pie chart shows the percentage of trials targeting specific cancers among the 29% of clinical trials that are cancer related. HIV, human immunodeficiency virus; HPV, human papillomavirus.
  5. Knowledge
  6. Knowledge