Difference between revisions of "Vaccines"

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[[Image:Syringe.jpg|right|thumb|200px|<p>'''Syringe'''</p>Source: Wikimedia Commons; Author: ZaldyImg (2008)]]
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{{toplink
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==Introduction==
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|linkpage =Immunology - WikiBlood
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Why do we vaccinate animals?
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|linktext =IMMUNOLOGY
 +
|thispagemap= Vaccines(Concept Map) - WikiBlood
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|pagetype =Blood
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}}
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 +
==Why Vaccinate?==
 +
 
 
*To protect against infectious diseases
 
*To protect against infectious diseases
−
*Where there is no effective treatment once infected e.g. FeLV, FIV
 
−
*Where disease is life-threatening e.g. Canine Parvovirus
 
−
*To prevent the spread of disease by virus excretion e.g. Rabies, FMDV
 
  
−
The goal is to vaccinate 90% of the population to reduce the amount of '''endemic''' virus until no new infections occur. Once the disease risk is low, vaccination can be replaced by an eradication or quarantine programme.
+
*Where there is no effective treatment once infected
 +
**E.g. [[Immunodeficiencies - WikiBlood#Feline Leukaemia Virus (FeLV)|FeLV]], FIV
 +
 
 +
*Where disease is life-threatening
 +
**E.g. Canine Parvovirus
 +
 
 +
*To prevent the spread of disease by virus excretion
 +
**E.g. Rabies, FMDV
 +
 
 +
*The goal is to vaccinate 90% of the population to reduce the amount of '''endemic''' virus until no new infections occur
 +
 
 +
*Once the disease risk is low, vaccination can be replaced by an eradication or quarantine programme  
  
 
==How do vaccines work?==
 
==How do vaccines work?==
−
Vaccination induces an immunological memory of the infectious organism. High levels of [[T cell differentiation#Cytotoxic T-Cells|cytotoxic T cells]] and neutralising [[Immunoglobulins - Overview|antibody]] are activated 24 - 48 hours post vaccination as a [[B cell differentiation#Secondary T Cell Dependent Response|secondary response]] (instead of 4-10 days later as a [[B cell differentiation#T-Cell Dependent Response|primary response]]). Neutralising [[Immunoglobulins|antibody]] then blocks the attachment of the infectious organism to host cell receptors.
 
  
−
'''Endogenous vaccines''' cause antigens to be made as new proteins by the cell, bacterium or virus and involves [[Major Histocompatability Complexes#MHC I|MHC class I]] processing live virus, recombinant virus or DNA vaccines.
+
*Vaccination sets up memory to the viral infection
  
−
'''Exogenous vaccines''' are when the antigen is processed from the outside by endocytosis without any new proteins being made by the host cell. This involves [[Major Histocompatability Complexes#MHC II|MHC class II]] processing inactivated and subunit vaccines.
+
*High levels of [[T cell differentiation - WikiBlood#Cytotoxic T-Cells|cytotoxic T cells]] and neutralising [[Immunoglobulins - WikiBlood|antibody]] are activated in 1-2 days as a [[B cell differentiation - WikiBlood#Secondary T Cell Dependent Response|secondary response]] (instead of 4-10 days as a [[B cell differentiation - WikiBlood#T-Cell Dependent Response|primary response]])
  
−
==Route of Administration==
+
*The infection is therefore prevented from taking hold causing lesions to develop
−
*Usually by subcutaneous injection for '''systemic''' protection. Some vaccines such as the [[Vaccinations_for_Rabbits#Myxomatosis_Vaccination|myxomatosis]] vaccine NobivacTM Myxo (Intervet UK Ltd) require an intradermal injection as part of the administration procedure.
 
−
*For a localised '''mucosal''' immune response, intranasal administration is required ([[Immunoglobulin A|IgA]]) e.g. kennel cough vaccine.
 
  
−
==Vaccination Options==
+
*Neutralising [[Immunoglobulins - WikiBlood|antibody]] blocks the attachment of virus to host cell receptors
−
[[Image:Passive Immunisation.jpg|thumb|right|200px|Passive Immunisation - Copyright nabrown RVC]]
+
 
 +
*'''Endogenous vaccines''' are where the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] are made as new proteins by the cell, bacterium or virus
 +
**Involves [[MHC - WikiBlood#MHC I|MHC class I]] processing
 +
**E.g. live virus, recombinant virus and DNA vaccines
 +
 
 +
*'''Exogenous vaccines''' are when the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] is processed from the outside by endocytosis without any new proteins being made by the host cell
 +
**involves [[MHC - WikiBlood#MHC II|MHC class II]] processing
 +
**E.g. Inactivated and subunit vaccines
 +
 
 +
==How do we vaccinate?==
 +
 
 +
*Usually by subcutaneous injection for '''systemic''' protection ([[Immunoglobulin G - WikiBlood|IgG]])
 +
 
 +
*For '''mucosal''' immune response, intranasal administration is best ([[Immunoglobulin A - WikiBlood|IgA]])
 +
 
 +
==What do we vaccinate with?==
 +
[[Image:Passive Immunisation.jpg|thumb|right|150px|Passive Immunisation - Copyright nabrown RVC]]
 
===Passive immunisation===
 
===Passive immunisation===
  
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'''Disadvantages:'''
 
'''Disadvantages:'''
−
*Short duration of action; temporary protection is obtained by the administration of preformed [[Immunoglobulins - Overview|antibody]] from another individual of the same or of a different species. The acquired antibodies are used in combination with [[Adaptive Immune System - Overview#Antigen Recognition|antigen]], and catabolised by the body, meaning protection is gradually lost over time
+
*Short duration of action
−
*Injection of antiserum may cause an [[Adverse Drug Reactions|allergic response]]
+
**Temporary protection by the administration of preformed [[Immunoglobulins - WikiBlood|antibody]] from another individual of the same or of a different species
−
*Antiserum contains many antibodies, not just the specific [[Immunoglobulins|antibodies]] needed
+
**The acquired [[Immunoglobulins - WikiBlood|antibodies]] are used in combination with [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]], and catabolised by the body, meaning protection is gradually lost
 +
*Injection of antiserum may cause an [[Allergic diseases - WikiClinical|allergic response]]
 +
*Antiserum contains many [[Immunoglobulins - WikiBlood|antibodies]], not just the specific [[Immunoglobulins - WikiBlood|antibodies]] needed
  
−
'''Types of antibodies administered:'''
+
'''Types of [[Immunoglobulins - WikiBlood|antibodies]] administered:'''
−
*Maternally-derived antibodies in [[Materno-Fetal Immunity - Introduction#Passive transfer via colostrum|colostrum]] when there is a [[Failure of Passive Transfer|failure of passive transfer]] of [[Immunoglobulin G]]
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*Maternally-derived [[Immunoglobulins - WikiBlood|antibodies]] in [[Materno-fetal immunity - WikiBlood#Passive transfer via colostrum|colostrum]]
−
*Antiserum  
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*Antiserum (artificial)
−
**The antibodies are used in combination with [[Adaptive Immune System - Overview#Antigen Recognition|antigen]] (and often an adjuvant) which is injected into a host animal
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**The [[Immunoglobulins - WikiBlood|antibodies]] are used in combination with [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] (and often an [[Vaccines - WikiBlood#Adjuvants|adjuvant]]) which is injected into the host animal
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**The immune system of that animal synthesises antibodies
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**The immune system of that animal synthesises [[Immunoglobulins - WikiBlood|antibodies]]
−
**Repeated injections at intervals increases total [[Immunoglobulins - Overview|antibody]] production
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**Repeated injections at intervals increases the total [[Immunoglobulins - WikiBlood|antibody]] production
−
**The immunised animal is bled and the serum collected which contains the newly made antibodies. The serum is called '''antiserum'''.
+
**The immunised animal is bled and the serum collected which contains the newly made [[Immunoglobulins - WikiBlood|antibodies]]. The serum is called '''antiserum'''.
 
**The serum can then be injected into a different animal to confer passive immunisation
 
**The serum can then be injected into a different animal to confer passive immunisation
  
 +
*Example of when passive immunisation is used:
 +
**Suspect tetanus
  
−
Examples of passive immunisation:
+
'''Passive Immunotherapy with Antibody'''
 
{| style="width:60%; height:200px" border="1" align=left
 
{| style="width:60%; height:200px" border="1" align=left
 
!INFECTION
 
!INFECTION
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| Used
 
| Used
 
| Not used
 
| Not used
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| Post-exposure to virus
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| Post-exposure to vaccine
 
|}
 
|}
 
<Br clear="left">
 
<Br clear="left">
 
<br>
 
<br>
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[[Image:Active Immunisation.jpg|thumb|right|200px|Active Immunisation - Copyright nabrown RVC]]
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[[Image:Active Immunisation.jpg|thumb|right|150px|Active Immunisation - Copyright nabrown RVC]]
  
 
===Active immunisation===
 
===Active immunisation===
−
Active immunisation requires the administration of antigen so the patient develops their own antibodies to protect against disease. Suitable antigens include:
+
*Administer [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] so the patient develops its own [[Immunoglobulins - WikiBlood|antibodies]] to protect against disease
−
*Living organisms
+
**Living organisms
−
*Dead organisms
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**Dead organisms
−
*Toxoids
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**Toxoids
−
*Subunit antigens
+
**Subunit antigens
−
*DNA
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**DNA
  
 
'''Advantages'''
 
'''Advantages'''
−
*Long duration of action; once antibody is produced against the antigen, [[B cell differentiation#Memory cells|memory cells]] are formed which continue circulating in the body
+
*Long duration of action  
 +
**Once [[Immunoglobulins - WikiBlood|antibody]] is produced against the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]], [[B cell differentiation - WikiBlood#Memory cells|memory cells]] are formed which continue circulating in the body
 +
**For further information on memory cells click [[B cell differentiation - WikiBlood|here]]
  
 
'''Disadvantages'''
 
'''Disadvantages'''
−
*The host's immune system needs to evoke an immune response against the antigen which can take a few days
+
*Delay in protection
−
*Can require two or more doses to be effective; the first dose initiates the '''priming''' reaction where antibody production ceases after a few weeks, but the second and subsequent doses create memory cells which remain in the circulation for a much longer period of time.
+
**The host's immune system needs to evoke an immune response against the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] which can take a few days
 +
**For further information on the [[Immunoglobulins - WikiBlood|antibody]] response click [[Adaptive Immune System - WikiBlood|here]]
 +
 
 +
*Often needs two or more doses  
 +
**The first dose initiates the '''priming''' reaction where [[Immunoglobulins - WikiBlood|antibody]] production ceases after a few weeks, but the second and subsequent doses create [[B cell differentiation - WikiBlood#Memory cells|memory cells]] which remain in the circulation for a much longer period of time
 +
**For further information on the T cell independent and dependent responses click [[B cell differentiation - WikiBlood#T-Cell Dependent and Independent Responses|here]]
 +
 
 +
==What antigen(s) do we use in the vaccine?==
  
−
==Vaccine Antigens==
 
−
Potential antigenic substances include:
 
 
===Whole Organism===
 
===Whole Organism===
−
'''Live Attenuated (LA) vaccines''' include the organism but in an altered form - virulent organisms cannot be used as vaccines as they have the potential to cause disease. Virulence is reduced by growing the organism in altered conditions (e.g. in cells or eggs), so that it is less able to replicate when introduced into the host, and is therefore less likely to cause disease. Virulence can also be reduced by genetic engineering, or by using naturally occurring avirulent strains.
 
  
 +
*Live attenuated organism
 +
**Virulent organisms cannot be used as vaccines as they would cause disease
 +
**Virulence is reduced by growing the organism in altered conditions (e.g. in cells or eggs), so that it is less able to replicate when introduced to the host, and therefore less likely to cause disease
 +
**Produces a superior response to disease than using killed organisms as the dose of [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] is larger and more sustained
 +
**Virulence can also be reduced by genetic engineering
 +
**Naturally occurring avirulent strains can also be used
 +
**Response takes place at the site of natural infection, producing a greater local response than with killed organism vaccines
 +
**E.g. The current vaccine for Tuberculosis (called BCG) contains an attenuated form of a mycobacteria
 +
**E.g. Vaccines for Leishmaniasis
 +
**E.g. Vaccines for parainfluenza virus 3 of calves is developed to be temperature-sensitive so that it grows at 34 C in the upper respiratory tract but not at 38 C in the lungs
 +
 +
*Killed inactivated organism or toxin (toxoid)
 +
**Virulent and toxic organisms cannot be used as vaccines as they would cause disease
 +
**Organisms can be killed using radiation or chemicals so that they still possess the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigens]] to stimulate an immune response, but the organisms are unable to replicate inside the host
 +
**Toxins are inactivated to produce a toxoid which will still have the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigens]] needed to produce an immune response but will not be harmful to the host
 +
**Needs two doses (for an explanation on the [[Lymphocytes - WikiBlood#T cells|T cell]] response click [[B cell differentiation - WikiBlood#T-Cell Dependent and Independent Responses|here]])
 +
**1:4000 formaldehyde is the current preparation
 +
**Inactivants containing azuridines and beta propiolactone are being developed which do not leave a persistent infectious viral fraction (like formaldehyde)
 +
 +
===Subunit Vaccine (part of the organism)===
 +
 +
*Purified protein
 +
**Single envelope protein separated from a purified virus by detergent then centrifuged (traditional method)
 +
**Genetic engineering can now make single protein vaccines
 +
 +
*Recombinant or synthetic protein
 +
**The gene for the [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] required is inserted into a virus vector or cloned into bacteria allowing endogenous expression
 +
**Small [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigens]], such as peptides, can be synthetically produced
 +
**E.g. Being developed constantly to fight the Influenza viruses
 +
**E.g. Canary pox vaccines encoding rabies or FeLV spike proteins (canary pox is safe as it undergoes incomplete replication in mammalian skin cells)
 +
 +
*DNA coding for proteins ([[Adaptive Immune System - WikiBlood#Antigen Recognition|antigens]])
 +
**Circular DNA plasmids expanded in disabled E.coli strains and then purified
 +
**Plasmids express the foreign gene insert at the site of injection
 +
**Can be vaccinated directly into the host
 +
 +
===Adjuvants===
 +
 +
*Used with vaccines containing inactivated organisms which alone only stimulate a weak immune response
  
−
LA vaccines produce a superior response to disease than using killed organisms as the dose of antigen is larger and more sustained, and the response takes place at the site of natural infection, producing a greater local response than with killed organism vaccines. Examples include:
+
*Some create a depot of [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] at the injection site allowing a steady flow of [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] into the afferent lymph
−
*The current vaccine for tuberculosis (called BCG) contains an attenuated form of a mycobacteria
 
−
*Vaccines for leishmaniasis
 
−
*Vaccines for parainfluenza virus 3 of calves is developed to be temperature-sensitive so that it grows at 34 C in the upper respiratory tract but not at 38 C in the lungs
 
  
−
'''Killed inactivated organism or toxin (toxoid)''' are useful where virulent and toxic organisms cannot be used as vaccines as they would cause disease. Organisms can be killed using radiation or chemicals so that they still possess the antigens to stimulate an immune response, but the organisms are unable to replicate inside the host. Alternatively, toxins are inactivated to produce a toxoid which will still have the antigens needed to produce an immune response but will not be harmful to the host. Two doses are required to [[B_cell_differentiation#Primary_T_Cell_Dependent_Response|'''prime''']] the immune system initially, and then induce an immunoligical [[B_cell_differentiation#Secondary_T_Cell_Dependent_Response|'''memory''']] of the disease causing organism.
+
*Some stimulate the immune system to amplify the adaptive immune response to [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigens]]
 +
**E.g. Pathogen-associated molecular patterns (PAMPs)
 +
**E.g. PAMP-like adjuvants which assist naive [[Lymphocytes - WikiBlood#T cells|T cell]] priming
  
−
1:4000 formaldehyde is used in the preparation of killed vaccines; inactivants containing azuridines and beta propiolactone are being developed which do not leave a persistent infectious viral fraction (like formaldehyde).
+
*Different subtypes of [[Lymphocytes - WikiBlood#Helper CD4+|T helper cells]] are stimulated by different adjuvants
 +
**E.g. Aluminium salts generate bias [[T cell differentiation - WikiBlood#TH2 Cells|T helper II]] responses for [[Immunoglobulins - WikiBlood|'''antibody''']]-mediated immunity
 +
**E.g. Killed mycobacteria generate IL-12 producing good '''cell'''-mediated immunity
  
−
===Subunits (part of the organism)===
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*Adjuvants decrease the number of injections needed and the amount of [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigen]] administered
−
These can be purified proteins such as a single envelope protein separated from a purified virus by detergent and then centrifuged (traditional method) - genetic engineering can now make single protein vaccines quickly and accurately.
 
  
−
Recombinant or synthetic proteins can also be used as a subunit - the gene for the antigen required is inserted into a virus vector or cloned into bacteria allowing endogenous expression of the antigen. Small antigens, such as peptides, can be produced synthetically where necessary e.g. with Influenza viruses that are constantly mutating, and Canary pox vaccines encoding rabies or FeLV spike proteins (canary pox is safe as it undergoes incomplete replication in mammalian skin cells).
+
===Marker Vaccines===
  
−
Subunit antigens can also be isolated using the DNA coding for antigenic proteins; circular DNA plasmids are expanded in disabled E.coli strains and then purified - the plasmids expressing the foreign gene can be vaccinated directly into the host.
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*Distinguish infected from vaccinated animals
  
−
==Adjuvants==
+
*Have a deleted protein or gene
−
Adjuvants are used with vaccines containing inactivated organisms which alone would only stimulate a weak immune response. Some adjuvants create a depot of antigen at the injection site allowing a steady flow of antigen into the afferent lymph, while others stimulate the immune system to amplify the adaptive immune response to antigens e.g. pathogen-associated molecular patterns (PAMPs). PAMP-like adjuvants assist naive [[T cells|T cell]] priming.
 
  
−
Different subtypes of [[T cell differentiation|T helper cells]] are stimulated by different adjuvants, for example:
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*Vaccinated animals cannot make antibody to the missing protein whereas infected animals can
−
*Aluminium salts generate bias [[T cell differentiation#TH2 Cells|T helper II]] responses for antibody-mediated immunity
 
−
*Killed mycobacteria generate IL-12 producing good '''cell'''-mediated immunity
 
  
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Adjuvants decrease the number of injections needed and the amount of antigen that needs to be administered, but they have been associated with vaccine reactions.
+
*Helps immunosurveillance for animals infected by a virus in countries that vaccinate against the virus
  
−
==Marker Vaccines==
+
==Which type of vaccine is used for each disease?==
−
Marker vaccines distinguish infected from vaccinated animals in disease control programmes.
 
−
They contain a deleted protein or gene; vaccinated animals cannot make antibody to the missing protein whereas infected animals can and this helps immunosurveillance for animals infected by an organism in countries that vaccinate against that disease.
 
  
−
==Tailoring Vaccines for Specific Diseases==
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*The life-cycle of the organisms needs to be understood to ascertain the best type of immune response for fighting the particular infection
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*The life-cycle of infectious organisms needs to be understood to ascertain the best type of immune response for fighting that particular infection
 
−
*A vaccine can be created to provide the specific immunity best suited for fighting the associated infection
 
  
−
===Immunity to Viral Infection===
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*A vaccine can be created to provide specific immunity which is best suited for fighting the specific infection
−
[[Image:Virus Life Cycle.jpg|thumb|right|200px|Virus Life Cycle - Copyright Dr Brian Catchpole BVetMed PhD MRCVS]]
 
−
The virus life cycle consists of an extracellular phase, a replicative intracellular phase and another extracellular phase spreading viral particles to other cells to begin the life cycle again
 
  
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Immunity for the extracellular phase requires neutralising [[Immunoglobulins - Overview|'''antibody''']]:
+
===Immunity to Virus Infection===
−
*[[B cells]] needed
+
[[Image:Virus Life Cycle.jpg|thumb|right|150px|Virus Life Cycle - Copyright Dr Brian Catchpole BVetMed PhD MRCVS]]
−
*[[T cell differentiation#TH2 Cells|T helper type II cells]] needed (for the [[Major Histocompatability Complexes#MHC II|MHC class II pathway]])
+
*The virus life cycle consists of an extracellular phase, a replicative intracellular phase and another extracellular phase spreading viral particles to other cells to begin the life cycle again
−
*Live, killed and subunit vaccines can be used
 
  
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Immunity for the intracellular phase requires [[T_cells#Cytotoxic_CD8.2B|CD8+ cytotoxic T lymphocytes (CTL)]] and uses the [[Major Histocompatability Complexes#MHC I|MHC class I pathway]].
+
*Immunity for the extracellular phase requires neutralising [[Immunoglobulins - WikiBlood|'''antibody''']]
−
*Only live vaccine can be used to get into cells (entering via the endogenous pathway)
+
**[[Lymphocytes - WikiBlood#B Cells|B cells]] needed
 +
**[[T cell differentiation - WikiBlood#TH2 Cells|T helper type II cells]] needed (for the [[MHC - WikiBlood#MHC II|MHC class II pathway]])
 +
**Live vaccine can be used
 +
**Killed vaccine can be used
 +
**Subunit vaccine can be used
 +
 
 +
*Immunity for the intracellular phase requires [[Lymphocytes - WikiBlood#Cytotoxic CD8+|'''CD8+ cytotoxic T cells''']]
 +
**[[MHC - WikiBlood#MHC I|MHC class I pathway]]
 +
**Only live vaccine can be used to get into cells (entering via the endogenous pathway)
  
 
===Immunity to Bacterial Infection===
 
===Immunity to Bacterial Infection===
  
−
*Extracellular bacterial infection needs antibody production for [[Complement#Opsonisation|opsonisation]] and to activate the [[Complement|complement pathways]]
+
*Extracellular bacterial infection needs [[Immunoglobulins - WikiBlood|'''antibody''']] production for [[Complement - WikiBlood#Opsonisation|opsonisation]] and to activate the [[Complement - WikiBlood|complement pathways]]
−
*[[B cells]] are needed
+
**[[Lymphocytes - WikiBlood#B Cells|B cells]] needed
−
*[[T cell differentiation#TH2 Cells|T helper type II cells]] are needed
+
**[[T cell differentiation - WikiBlood#TH2 Cells|T helper type II cells]] needed
  
−
Vesicular infections can only be cured by organisms being destroyed inside [[Macrophages|'''macrophages''']]
+
*Vesicular infections can only be cured by organisms being destroyed inside [[Macrophages - WikiBlood|'''macrophages''']]
−
*[[T cell differentiation#TH1 Cells|T helper type I cells]] are needed
+
**[[T cell differentiation - WikiBlood#TH1 Cells|T helper type I cells]] needed
  
 
==When do we vaccinate?==
 
==When do we vaccinate?==
−
[[Image:Colostrum Intake.jpg|right|thumb|200px|Colostrum Intake - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
+
[[Image:Colostrum Intake.jpg|right|thumb|150px|Colostrum Intake - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
−
[[Image:Vaccinating puppies with Parvo.jpg|right|thumb|200px|Response to vaccination against canine parvovirus depending on antibody titre of puppies - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
+
[[Image:Vaccinating puppies with Parvo.jpg|right|thumb|150px|Response to vaccination against canine parvovirus depending on antibody titre of puppies - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
−
*Breeding females can be vaccinated so that immunity is passively transferred to their offspring via the [[Materno-Fetal Immunity - Introduction#Passive transfer via colostrum|colostrum]] - this protects neonates for the first 8-12 weeks of life.
+
*Usually when animals are young
 +
 
 +
*Breeding females so immunity is passed to offspring via the [[Materno-fetal immunity - WikiBlood#Passive transfer via colostrum|colostrum]]
 +
**Protects neonates for the first 8-12 weeks of life
  
−
*Vaccination of young animals should be when the natural passive immunity decreases below the threshold for providing protection. Active immunity should then be stimulated so that the animal has sustained protection. If vaccination is given too early, the natural immunity can interfere with immunisation by binding and neutralising the vaccine antigens.
+
*Vaccination of young animals should be when the natural passive immunity decreases below the threshold for providing protection. Active immunity should then be stimulated so that the animal has constant protection. The vaccination should not be given too early, as the natural immunity can interfere with immunisation by binding and neutralising the vaccine [[Adaptive Immune System - WikiBlood#Antigen Recognition|antigens]].
  
−
*Two vaccines are usually given to allow for differences between individual animals in the time taken for any natural immunity to decrease.
+
*2 vaccines are usually given to allow for differences between neonates, as the point where natural immunity decreases and active immunity needs to be stimulated, will differ between littermates and between different animals
  
 
===Dog Vaccinations===
 
===Dog Vaccinations===
−
Diseases routinely covered by vaccination include:
 
  
−
*[[Canine Parvovirus]]
+
'''Diseases covered by Vaccination'''
 +
 
 +
*Canine [[Parvoviridae|Parvovirus]]
  
−
*[[Canine Distemper Virus|Canine Distemper]]
+
*Canine Distemper
  
−
*[[Infectious Canine Hepatitis]]
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*Canine Infectious Hepatitis
  
−
*[[Leptospirosis - Cats and Dogs|Leptospirosis]]
+
*Leptospirosis
  
−
*[[Canine Parainfluenza - 2|Canine Parainfluenza virus]]
+
*Canine Parainfluenza virus
  
−
*[[Canine Infectious Tracheobronchitis|Kennel Cough]]
+
*Kennel Cough  
  
−
*[[Rabies]]
+
*Rabies  
  
 
'''When to Vaccinate'''
 
'''When to Vaccinate'''
  
−
Puppies are usually first vaccinated between 6 to 8 weeks of age; a second vaccination is given 3-4 weeks later. Younger puppies (less than 16 weeks old) may require the third booster 3-4 weeks later, making the vaccination schedule to end between 14 to 16 weeks old. Adult dogs need booster vaccination regularly (depending on the specific vaccination and the recommendations of the vaccine manufacturer).
+
*Puppies are usually first vaccinated between 6 to 8 weeks of age
 +
**A second vaccination is needed 2 weeks later
 +
 
 +
*Adult dogs need booster vaccination regularly (depending on the specific vaccination)
  
 
===Cat Vaccinations===
 
===Cat Vaccinations===
−
[[Image:Sebby cat.jpg|thumb|right|175px|Cat - Copyright nabrown RVC]]
+
[[Image:Sebby cat.jpg|thumb|right|150px|Cat - Copyright nabrown RVC]]
 
'''Diseases covered by Vaccination'''
 
'''Diseases covered by Vaccination'''
  
−
*Feline Infectious Enteritis ([[Feline Panleucopenia]])
+
*Feline Infectious Enteritis ([[Feline Parvovirus]])
  
−
*'Cat Flu', including Feline [[Feline Herpesvirus 1|Herpesvirus]] and [[Feline Calicivirus]]
+
*Feline Infectious Respiratory Disease 'Cat Flu'
 +
**Feline [[Herpesviridae|Herpesvirus]]
 +
**Feline [[Caliciviridae|Calicivirus]]
  
−
*[[Feline Leukaemia Virus]] (FeLV)
+
*[[Immunodeficiencies - WikiBlood#Feline Leukaemia Virus (FeLV)|Feline Leukaemia virus]]
 +
**Killed whole virus (only used in USA)
 +
**Purified subunit
 +
**Recombinant subunit
 +
**Recombinant canarypox
  
−
*[[Feline Immunodeficiency Virus]]  
+
*[[Immunodeficiencies - WikiBlood#Feline Immunodeficiency Virus (FIV)|Feline Infectious Viraemia]]  
 +
**Killed whole virus containing A and D subtypes (only used in USA)
  
−
* [[Chlamydiosis, Feline|Feline chlamydiosis]] (Chlamydophila felis)
+
*Feline [[Chlamydophilosis]]  
  
 
'''When to Vaccinate'''
 
'''When to Vaccinate'''
−
Kittens are usually vaccinated around 9 weeks old and a second vaccination is given 3 weeks later. Adult cats need booster vaccination regularly (depending on the specific vaccination and the vaccine manufacturers recommendations).
+
 
 +
*Kittens are usually vaccinated around 9 weeks old
 +
**A second vaccination is needed 3 weeks later
 +
 
 +
*Adult cats need booster vaccination regularly (depending on the specific vaccination)
  
 
===Rabbit Vaccinations===
 
===Rabbit Vaccinations===
−
[[Image:Buzz bunny.jpg|thumb|right|200px|Rabbit - Copywright L. Drew RVC]]
+
[[Image:Buzz bunny.jpg|thumb|right|150px|Rabbit - Copywright L. Drew RVC]]
 
'''Diseases covered by Vaccination'''
 
'''Diseases covered by Vaccination'''
  
−
*[[Vaccinations_for_Rabbits#VHD_Vaccination|Viral Haemorrhagic Disease]]
+
*Viral Haemorrhagic Disease
  
−
*[[Vaccinations_for_Rabbits#Myxomatosis_Vaccination|Myxomatosis]]
+
*[[Poxviruses#Leporipoxviruses|Myxomatosis]]
  
 
'''When to Vaccinate'''
 
'''When to Vaccinate'''
−
Rabbits can be vaccinated against [[Myxomatosis|myxomatosis]] from 6 weeks of age and VHD from 2½ to 3 months of age. Booster vaccinations are given every 12 months. In areas at high risk of myxomatosis, it is recommended to give myxomatosis boosters at six-monthly intervals. Some myxomatosis vaccines need to given [[Vaccinations_for_Rabbits#Myxomatosis_Vaccination|partially intradermally]].
 
  
−
==Vaccine Failure==
+
*Rabbits can be vaccinated against [[Poxviruses#Leporipoxviruses|Myxomatosis]] from 6 weeks of age
−
Failures do occur and should be reported on the VMD [http://www.vmd.gov.uk/ 'yellow form' MLA252A] if the events occur in the United Kingdom. Vaccine failures in other European Union (EU) Member States, Norway, Iceland and Liechtenstein should be reported to the relevant competent authority where the event occurred using the [http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000176.jsp&mid=WC0b01ac058002ddcb/ EU reporting forms for veterinarians] which are available in each EU language on the [http://www.ema.europa.eu/ European Medicines Agency] website. Circumstances leading to vaccine failures include:
+
 
−
*Recipient is already infected with the virus or is immunosuppressed and unable to mount an immune response.
+
*HVD from 2½ to 3 months of age 
  
−
*Break down of the '''cold-chain''' during transport (incorrect storage of vaccines requiring refrigeration)
+
*Booster vaccinations are given every 12 months. In areas at high risk of myxomatosis, it is recommended to give myxomatosis boosters at six-monthly intervals.
  
−
*Improper administration (e.g.myxomatosis vaccine)
+
==Vaccine Failure==
  
−
*Accidental mixing of inactivated and live vaccines in the same syringe
+
*Recipient is already infected with the virus or immunosuppressed
  
−
*Recipient has maternal antibody to the vaccine
+
*Break down of the '''cold-chain''' during transport
  
−
*Immunity waning due to missed booster vaccination
+
*Improper administration
  
−
*Vaccine is damaged during manufacture
+
*Mixing of inactivated and live vaccines in the same syringe
  
−
{{Learning
+
*Recipient has maternal antibody to the vaccine
−
|flashcards = [[Vaccination Flashcards|Vaccination Flashcards]]
 
−
|full text =[http://www.cabi.org/cabdirect/FullTextPDF/2009/20093258316.pdf '''Factors influencing vaccine efficacy - a general review.''' Rashid, A.; Rasheed, K.; Akhtar, M.; Pakistan Agricultural Scientists Forum, Lahore, Pakistan, JAPS, Journal of Animal and Plant Sciences, 2009, 19, 1, pp 22-25, 18 ref.]
 
  
−
[http://www.cabi.org/cabdirect/FullTextPDF/2009/20093115229.pdf ''' Establishing vaccine protocols - focus on client communication.''' Datz, C.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Orlando, Florida, USA, 17-21 January, 2009, 2009, pp 608-611]
+
*Not enough animals vaccinated
  
−
[http://www.cabi.org/cabdirect/FullTextPDF/2009/20093115232.pdf '''Feline lifestyle vaccination protocols.''' Lappin, M. R.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Orlando, Florida, USA, 17-21 January, 2009, 2009, pp 621-624, 18 ref.]
+
*Boosters not done
  
−
[http://www.cabi.org/cabdirect/FullTextPDF/2007/20073166574.pdf '''Immunological basis of vaccination.''' Lunn, D. P.; The North American Veterinary Conference, Gainesville, USA, Large animal. Proceedings of the North American Veterinary Conference, Volume 21, Orlando, Florida, USA, 2007, 2007, pp 135-137]
+
*Vaccine is counterfeit or homeopathic
  
−
[http://www.cabi.org/cabdirect/FullTextPDF/2007/20073166575.pdf '''Equine vaccines: what works, what doesn't?''' Lunn, D. P.; The North American Veterinary Conference, Gainesville, USA, Large animal. Proceedings of the North American Veterinary Conference, Volume 21, Orlando, Florida, USA, 2007, 2007, pp 138-140]
+
==Links==
  
−
|Vetstream = [https://www.vetstream.com/canis/Content/Freeform/fre00859.asp Vaccination Protocol]
+
*[[Clinical Case 3|Myxomatosis Clinical Case]]
−
}}
 
  
−
==Links==
+
*[[Viruses|Viruses A to Z]]
−
:[[:Category:Viral Organisms|Viruses A to Z]]
 
−
:[[:Category:Bacterial Organisms|Bacteria A to Z]]
 
  
 
==References==
 
==References==
  
 
'''Textbooks'''
 
'''Textbooks'''
 +
 
*Ivan Roitt: '''Essential Immunology,''' Ninth edition
 
*Ivan Roitt: '''Essential Immunology,''' Ninth edition
  
 
'''Lecture Notes'''
 
'''Lecture Notes'''
 +
 
*Dr Brian Catchpole BVetMed PhD MRCVS
 
*Dr Brian Catchpole BVetMed PhD MRCVS
 +
 
*Dr Peter H Russell BVSc MSc PhD MRCVS FRCPath
 
*Dr Peter H Russell BVSc MSc PhD MRCVS FRCPath
  
−
<br><br>
+
==Creators==
−
{{Jim Bee 2007}}
+
 
−
[[Category:Immunology]]
+
[[Natalie Brown]]
 +
 
 +
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 +
<big><center>[[Host invasion by microorganisms - WikiBlood|'''BACK TO HOST INVASION BY MICROORGANISMS''']]</center></big>

Revision as of 17:04, 5 September 2009

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Why Vaccinate?

  • To protect against infectious diseases
  • Where there is no effective treatment once infected
  • Where disease is life-threatening
    • E.g. Canine Parvovirus
  • To prevent the spread of disease by virus excretion
    • E.g. Rabies, FMDV
  • The goal is to vaccinate 90% of the population to reduce the amount of endemic virus until no new infections occur
  • Once the disease risk is low, vaccination can be replaced by an eradication or quarantine programme

How do vaccines work?

  • Vaccination sets up memory to the viral infection
  • The infection is therefore prevented from taking hold causing lesions to develop
  • Neutralising antibody blocks the attachment of virus to host cell receptors
  • Endogenous vaccines are where the antigen are made as new proteins by the cell, bacterium or virus
    • Involves MHC class I processing
    • E.g. live virus, recombinant virus and DNA vaccines
  • Exogenous vaccines are when the antigen is processed from the outside by endocytosis without any new proteins being made by the host cell
    • involves MHC class II processing
    • E.g. Inactivated and subunit vaccines

How do we vaccinate?

  • Usually by subcutaneous injection for systemic protection (IgG)
  • For mucosal immune response, intranasal administration is best (IgA)

What do we vaccinate with?

Passive Immunisation - Copyright nabrown RVC

Passive immunisation

Advantages

  • Immediate protection

Disadvantages:

  • Short duration of action
    • Temporary protection by the administration of preformed antibody from another individual of the same or of a different species
    • The acquired antibodies are used in combination with antigen, and catabolised by the body, meaning protection is gradually lost
  • Injection of antiserum may cause an allergic response
  • Antiserum contains many antibodies, not just the specific antibodies needed

Types of antibodies administered:

  • Maternally-derived antibodies in colostrum
  • Antiserum (artificial)
    • The antibodies are used in combination with antigen (and often an adjuvant) which is injected into the host animal
    • The immune system of that animal synthesises antibodies
    • Repeated injections at intervals increases the total antibody production
    • The immunised animal is bled and the serum collected which contains the newly made antibodies. The serum is called antiserum.
    • The serum can then be injected into a different animal to confer passive immunisation
  • Example of when passive immunisation is used:
    • Suspect tetanus

Passive Immunotherapy with Antibody

INFECTION HUMAN SOURCE OF ANTIBODY EQUINE SOURCE OF ANTIBODY USE
Tetanus Diptheria Used Used Prophylaxis treatment
Botulism Not used Used Treatment
Venomous bite Not used Used Treatment
Rabies Used Not used Post-exposure to vaccine



Active Immunisation - Copyright nabrown RVC

Active immunisation

  • Administer antigen so the patient develops its own antibodies to protect against disease
    • Living organisms
    • Dead organisms
    • Toxoids
    • Subunit antigens
    • DNA

Advantages

  • Long duration of action
    • Once antibody is produced against the antigen, memory cells are formed which continue circulating in the body
    • For further information on memory cells click here

Disadvantages

  • Delay in protection
    • The host's immune system needs to evoke an immune response against the antigen which can take a few days
    • For further information on the antibody response click here
  • Often needs two or more doses
    • The first dose initiates the priming reaction where antibody production ceases after a few weeks, but the second and subsequent doses create memory cells which remain in the circulation for a much longer period of time
    • For further information on the T cell independent and dependent responses click here

What antigen(s) do we use in the vaccine?

Whole Organism

  • Live attenuated organism
    • Virulent organisms cannot be used as vaccines as they would cause disease
    • Virulence is reduced by growing the organism in altered conditions (e.g. in cells or eggs), so that it is less able to replicate when introduced to the host, and therefore less likely to cause disease
    • Produces a superior response to disease than using killed organisms as the dose of antigen is larger and more sustained
    • Virulence can also be reduced by genetic engineering
    • Naturally occurring avirulent strains can also be used
    • Response takes place at the site of natural infection, producing a greater local response than with killed organism vaccines
    • E.g. The current vaccine for Tuberculosis (called BCG) contains an attenuated form of a mycobacteria
    • E.g. Vaccines for Leishmaniasis
    • E.g. Vaccines for parainfluenza virus 3 of calves is developed to be temperature-sensitive so that it grows at 34 C in the upper respiratory tract but not at 38 C in the lungs
  • Killed inactivated organism or toxin (toxoid)
    • Virulent and toxic organisms cannot be used as vaccines as they would cause disease
    • Organisms can be killed using radiation or chemicals so that they still possess the antigens to stimulate an immune response, but the organisms are unable to replicate inside the host
    • Toxins are inactivated to produce a toxoid which will still have the antigens needed to produce an immune response but will not be harmful to the host
    • Needs two doses (for an explanation on the T cell response click here)
    • 1:4000 formaldehyde is the current preparation
    • Inactivants containing azuridines and beta propiolactone are being developed which do not leave a persistent infectious viral fraction (like formaldehyde)

Subunit Vaccine (part of the organism)

  • Purified protein
    • Single envelope protein separated from a purified virus by detergent then centrifuged (traditional method)
    • Genetic engineering can now make single protein vaccines
  • Recombinant or synthetic protein
    • The gene for the antigen required is inserted into a virus vector or cloned into bacteria allowing endogenous expression
    • Small antigens, such as peptides, can be synthetically produced
    • E.g. Being developed constantly to fight the Influenza viruses
    • E.g. Canary pox vaccines encoding rabies or FeLV spike proteins (canary pox is safe as it undergoes incomplete replication in mammalian skin cells)
  • DNA coding for proteins (antigens)
    • Circular DNA plasmids expanded in disabled E.coli strains and then purified
    • Plasmids express the foreign gene insert at the site of injection
    • Can be vaccinated directly into the host

Adjuvants

  • Used with vaccines containing inactivated organisms which alone only stimulate a weak immune response
  • Some create a depot of antigen at the injection site allowing a steady flow of antigen into the afferent lymph
  • Some stimulate the immune system to amplify the adaptive immune response to antigens
    • E.g. Pathogen-associated molecular patterns (PAMPs)
    • E.g. PAMP-like adjuvants which assist naive T cell priming
  • Different subtypes of T helper cells are stimulated by different adjuvants
    • E.g. Aluminium salts generate bias T helper II responses for antibody-mediated immunity
    • E.g. Killed mycobacteria generate IL-12 producing good cell-mediated immunity
  • Adjuvants decrease the number of injections needed and the amount of antigen administered

Marker Vaccines

  • Distinguish infected from vaccinated animals
  • Have a deleted protein or gene
  • Vaccinated animals cannot make antibody to the missing protein whereas infected animals can
  • Helps immunosurveillance for animals infected by a virus in countries that vaccinate against the virus

Which type of vaccine is used for each disease?

  • The life-cycle of the organisms needs to be understood to ascertain the best type of immune response for fighting the particular infection
  • A vaccine can be created to provide specific immunity which is best suited for fighting the specific infection

Immunity to Virus Infection

Virus Life Cycle - Copyright Dr Brian Catchpole BVetMed PhD MRCVS
  • The virus life cycle consists of an extracellular phase, a replicative intracellular phase and another extracellular phase spreading viral particles to other cells to begin the life cycle again

Immunity to Bacterial Infection

When do we vaccinate?

Colostrum Intake - Copyright Prof Dirk Werling DrMedVet PhD MRCVS
Response to vaccination against canine parvovirus depending on antibody titre of puppies - Copyright Prof Dirk Werling DrMedVet PhD MRCVS
  • Usually when animals are young
  • Breeding females so immunity is passed to offspring via the colostrum
    • Protects neonates for the first 8-12 weeks of life
  • Vaccination of young animals should be when the natural passive immunity decreases below the threshold for providing protection. Active immunity should then be stimulated so that the animal has constant protection. The vaccination should not be given too early, as the natural immunity can interfere with immunisation by binding and neutralising the vaccine antigens.
  • 2 vaccines are usually given to allow for differences between neonates, as the point where natural immunity decreases and active immunity needs to be stimulated, will differ between littermates and between different animals

Dog Vaccinations

Diseases covered by Vaccination

  • Canine Distemper
  • Canine Infectious Hepatitis
  • Leptospirosis
  • Canine Parainfluenza virus
  • Kennel Cough
  • Rabies

When to Vaccinate

  • Puppies are usually first vaccinated between 6 to 8 weeks of age
    • A second vaccination is needed 2 weeks later
  • Adult dogs need booster vaccination regularly (depending on the specific vaccination)

Cat Vaccinations

Cat - Copyright nabrown RVC

Diseases covered by Vaccination

  • Feline Leukaemia virus
    • Killed whole virus (only used in USA)
    • Purified subunit
    • Recombinant subunit
    • Recombinant canarypox

When to Vaccinate

  • Kittens are usually vaccinated around 9 weeks old
    • A second vaccination is needed 3 weeks later
  • Adult cats need booster vaccination regularly (depending on the specific vaccination)

Rabbit Vaccinations

Rabbit - Copywright L. Drew RVC

Diseases covered by Vaccination

  • Viral Haemorrhagic Disease

When to Vaccinate

  • Rabbits can be vaccinated against Myxomatosis from 6 weeks of age
  • HVD from 2½ to 3 months of age
  • Booster vaccinations are given every 12 months. In areas at high risk of myxomatosis, it is recommended to give myxomatosis boosters at six-monthly intervals.

Vaccine Failure

  • Recipient is already infected with the virus or immunosuppressed
  • Break down of the cold-chain during transport
  • Improper administration
  • Mixing of inactivated and live vaccines in the same syringe
  • Recipient has maternal antibody to the vaccine
  • Not enough animals vaccinated
  • Boosters not done
  • Vaccine is counterfeit or homeopathic

Links

References

Textbooks

  • Ivan Roitt: Essential Immunology, Ninth edition

Lecture Notes

  • Dr Brian Catchpole BVetMed PhD MRCVS
  • Dr Peter H Russell BVSc MSc PhD MRCVS FRCPath

Creators

Natalie Brown

BACK TO IMMUNOLOGY
BACK TO HOST INVASION BY MICROORGANISMS
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