Difference between revisions of "Vaccines"

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<big><center>[[Immunology - WikiBlood|'''BACK TO IMMUNOLOGY''']]</center></big>
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[[Image:Syringe.jpg|right|thumb|200px|<p>'''Syringe'''</p>Source: Wikimedia Commons; Author: ZaldyImg (2008)]]
<big><center>[[Host invasion by microorganisms - WikiBlood|'''BACK TO HOST INVASION BY MICROORGANISMS''']]</center></big>
+
==Introduction==
 +
Why do we vaccinate animals?
 +
*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.
  
==Why Vaccinate?==
+
==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.
  
*To protect against infectious diseases
+
'''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.
  
*Where there is no effective treatment once infected
+
'''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.
**E.g. FeLV, FIV
 
  
*Where disease is life-threatening
+
==Route of Administration==
**E.g. Canine Parvovirus
+
*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.
  
*To prevent the spread of disease
+
==Vaccination Options==
**E.g. Rabies, FMDV
+
[[Image:Passive Immunisation.jpg|thumb|right|200px|Passive Immunisation - Copyright nabrown RVC]]
 +
===Passive immunisation===
  
==How do we vaccinate?==
+
'''Advantages'''
 +
*Immediate protection
  
*Usually by subcutaneous injection for '''systemic''' protection ([[Immunoglobulin G - WikiBlood|IgG]])
+
'''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
 +
*Injection of antiserum may cause an [[Adverse Drug Reactions|allergic response]]
 +
*Antiserum contains many antibodies, not just the specific [[Immunoglobulins|antibodies]] needed
  
*For '''mucosal''' immune reponse, intranasal administration is best ([[Immunoglobulin A - WikiBlood|IgA]])
+
'''Types of 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]]
 +
*Antiserum
 +
**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
 +
**The immune system of that animal synthesises antibodies
 +
**Repeated injections at intervals increases total [[Immunoglobulins - Overview|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
  
==What do we vaccinate with?==
 
[[Image:Passive Immunisation.jpg|thumb|right|150px|Passive Immunisation - Copyright nabrown RVC]]
 
'''Passive immunisation'''
 
*Administer antibodies
 
**Maternally-derived antibodies in colostrum
 
**Antiserum (artificial)
 
  
*Immediate protection
+
Examples of passive immunisation:
 +
{| style="width:60%; height:200px" border="1" align=left
 +
!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 virus
 +
|}
 +
<Br clear="left">
 +
<br>
 +
[[Image:Active Immunisation.jpg|thumb|right|200px|Active Immunisation - Copyright nabrown RVC]]
  
*Short duration of action
+
===Active immunisation===
[[Image:Active Immunisation.jpg|thumb|right|150px|Active Immunisation - Copyright nabrown RVC]]
+
Active immunisation requires the administration of antigen so the patient develops their own antibodies to protect against disease. Suitable antigens include:
'''Active immunisation'''
+
*Living organisms
*Administer antigen so the patient's own antibodies protect against disease
+
*Dead organisms
**Living organisms
+
*Toxoids
**Dead organisms
+
*Subunit antigens
**Toxoids
+
*DNA
**Subunit antigens
 
**DNA
 
  
*Delay in protection
+
'''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
  
*Often needs two or more doses
+
'''Disadvantages'''
 +
*The host's immune system needs to evoke an immune response against the antigen which can take a few days
 +
*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.
  
*Long duration of action
+
==Vaccine Antigens==
 +
Potential antigenic substances include:
 +
===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.
  
==What antigen(s) do we use in the vaccine?==
 
  
===Whole Organsim===
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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:
 +
*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
  
*Live attenuated organism
+
'''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.
**Virulent organisms cannot be used as vaccines as they would cause disease
 
**Virulence is reduced by growing the organism in altered conditions so that it is less able to replicate when introduced to the host and therefore less likely to cause disease
 
  
*Killed inactivated organism or toxin (toxoid)
+
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).
**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 posess 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 reponse but will not be harmful to the host
 
**Needs two doses
 
  
===Subunit Vaccine (part of the organism)===
+
===Subunits (part of the organism)===
 +
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.
  
*Purified protein
+
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).
**From lysed organisms
 
  
*Recombinant or synthetic protein
+
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.
**The gene for the antigen required is inserted into a virus vector or cloned into bacteria
 
**Small antigens, such as peptides can be synthetically produced
 
  
*DNA coding for proteins (antigens)
+
==Adjuvants==
**Can be vaccinated directly into the host
+
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.
  
===Adjuvants===
+
Different subtypes of [[T cell differentiation|T helper cells]] are stimulated by different adjuvants, for example:
 +
*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
  
*Used with vaccines containing inactivated organisms which alone only stimulate a weak immune response
+
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.
  
*Some create a depot of antigen at the injection site allowing a steady flow of antigen into the afferent lymph
+
==Marker Vaccines==
 +
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.
  
*Some stimulate the immune system to amplify the adaptive immune reponse to antigens
+
==Tailoring Vaccines for Specific Diseases==
**E.g. Pathogen-associated molecular patterns (PAMPs)
+
*The life-cycle of infectious organisms needs to be understood to ascertain the best type of immune response for fighting that particular infection
**E.g. PAMP-like adjuvants which assist naive T cell priming
+
*A vaccine can be created to provide the specific immunity best suited for fighting the associated infection
  
*Different subtypes of T helper cells are stimulated by different adjuvants
+
===Immunity to Viral Infection===
**E.g. Aluminium salts generate bias T helper II reponses for '''antibody'''-mediated immunity
+
[[Image:Virus Life Cycle.jpg|thumb|right|200px|Virus Life Cycle - Copyright Dr Brian Catchpole BVetMed PhD MRCVS]]
**E.g. Killed mycobacteria generate IL-12 producing good '''cell'''-mediated immunity
+
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
  
==Which type of vaccine is used for each disease?==
+
Immunity for the extracellular phase requires neutralising [[Immunoglobulins - Overview|'''antibody''']]:
 +
*[[B cells]] needed
 +
*[[T cell differentiation#TH2 Cells|T helper type II cells]] needed (for the [[Major Histocompatability Complexes#MHC II|MHC class II pathway]])
 +
*Live, killed and subunit vaccines can be used
  
*The life-cycle of the organisms needs to be understood to ascertain the best type of immune reponse for fighting the particular infection
+
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]].
 +
*Only live vaccine can be used to get into cells (entering via the endogenous pathway)
  
*A vaccine can be created to provide specific immunity which is best suited for fighting the specific infection
+
===Immunity to Bacterial Infection===
  
===Immunity to Virus Infection===
+
*Extracellular bacterial infection needs antibody production for [[Complement#Opsonisation|opsonisation]] and to activate the [[Complement|complement pathways]]
 +
*[[B cells]] are needed
 +
*[[T cell differentiation#TH2 Cells|T helper type II cells]] are needed
  
*The virus life cycle consists of an extracellular phase, a replicative intracellular phase and another extracellular phase spreading virual particles to other cells to begin the life cycle again
+
Vesicular infections can only be cured by organisms being destroyed inside [[Macrophages|'''macrophages''']]
 +
*[[T cell differentiation#TH1 Cells|T helper type I cells]] are needed
  
*Immunity for the extracellular phase requires neutralising '''antibody'''
+
==When do we vaccinate?==
**B cells needed
+
[[Image:Colostrum Intake.jpg|right|thumb|200px|Colostrum Intake - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
**T helper type II cells needed (for the MHC class II pathway)
+
[[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]]
**Live vaccine can be used
+
*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.
**Killed vaccine can be used
 
**Subunit vaccine can be used
 
  
*Immunity for the intracellular phase requires '''CD8+ cytotoxic T cells'''
+
*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.
**MHC class I pathway
 
**Only live vaccine can be used to get into cells (entering via the endogenous pathway)
 
  
===Immunity to Bacterial Infection===
+
*Two vaccines are usually given to allow for differences between individual animals in the time taken for any natural immunity to decrease.
  
*Extracellular bacterial infection need '''antibody''' production for opsonisation and to activate the complement pathways
+
===Dog Vaccinations===
**B cells needed
+
Diseases routinely covered by vaccination include:
**T helper type II cells needed
 
  
*Vesicular infections can only be cured by organisms being destroyed inside '''macrophages'''
+
*[[Canine Parvovirus]]
**T helper type I cells needed
 
  
==When do we Vaccinate?==
+
*[[Canine Distemper Virus|Canine Distemper]]
  
*Usually when animals are young
+
*[[Infectious Canine Hepatitis]]
  
*Breeding females so immunity is passed to offspring via the colostrum
+
*[[Leptospirosis - Cats and Dogs|Leptospirosis]]
**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.
+
*[[Canine Parainfluenza - 2|Canine Parainfluenza virus]]
  
*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
+
*[[Canine Infectious Tracheobronchitis|Kennel Cough]]
  
===Dog Vaccinations===
+
*[[Rabies]]
  
'''Diseases covered by Vaccination'''
+
'''When to Vaccinate'''
  
*Canine Parvovirus
+
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).
  
*Canine Distemper
+
===Cat Vaccinations===
 +
[[Image:Sebby cat.jpg|thumb|right|175px|Cat - Copyright nabrown RVC]]
 +
'''Diseases covered by Vaccination'''
  
*Canine Infectious Hepatitis
+
*Feline Infectious Enteritis ([[Feline Panleucopenia]])
  
*Leptospirosis
+
*'Cat Flu', including Feline [[Feline Herpesvirus 1|Herpesvirus]] and [[Feline Calicivirus]]
  
*Canine Parainfluenza virus
+
*[[Feline Leukaemia Virus]] (FeLV)
  
*Kennel Cough (optional)
+
*[[Feline Immunodeficiency Virus]]
  
*Rabies (optional)
+
* [[Chlamydiosis, Feline|Feline chlamydiosis]] (Chlamydophila felis)
  
 
'''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).
  
*Puppies are usually vaccinated between 6 to 8 weeks of age
+
===Rabbit Vaccinations===
**A second vaccination is needed 2 weeks later
+
[[Image:Buzz bunny.jpg|thumb|right|200px|Rabbit - Copywright L. Drew RVC]]
 
 
*Adult dogs need booster vaccination regularly (depending on the specific vaccination)
 
 
 
===Cat Vaccinations===
 
 
 
 
'''Diseases covered by Vaccination'''
 
'''Diseases covered by Vaccination'''
  
*Feline Infectious Enteritis
+
*[[Vaccinations_for_Rabbits#VHD_Vaccination|Viral Haemorrhagic Disease]]
  
*Feline Infectious Respiratory Disease 'Cat Flu'
+
*[[Vaccinations_for_Rabbits#Myxomatosis_Vaccination|Myxomatosis]]
**Feline Herpesvirus
 
**Feline Calicivirus
 
  
*Feline Leukaemia virus
+
'''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]].
  
*Feline Infectious Viraemia virus
+
==Vaccine Failure==
 +
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.
  
*Feline Chlamydophilosis (optional)
+
*Break down of the '''cold-chain''' during transport (incorrect storage of vaccines requiring refrigeration)
  
'''When to Vaccinate'''
+
*Improper administration (e.g.myxomatosis vaccine)
  
*Kittens are usually vaccinated around 9 weeks old
+
*Accidental mixing of inactivated and live vaccines in the same syringe
**A second vaccination is needed 3 weeks later
 
  
*Adult cats need booster vaccination regularly (depending on the specific vaccination)
+
*Recipient has maternal antibody to the vaccine
  
===Rabbit Vaccinations===
+
*Immunity waning due to missed booster vaccination
  
'''Diseases covered by Vaccination'''
+
*Vaccine is damaged during manufacture
  
*Viral Haemorrhagic Disease
+
{{Learning
 +
|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.]
  
*Myxomatosis
+
[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]
  
'''When to Vaccinate'''
+
[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.]
  
*Rabbits can be vaccinated against Myxomatosis from 6 weeks of age
+
[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]
  
*HVD from 2½ to 3 months of age 
+
[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]
  
*Booster vaccinations are given every 12 months
+
|Vetstream = [https://www.vetstream.com/canis/Content/Freeform/fre00859.asp Vaccination Protocol]
 +
}}
  
 
==Links==
 
==Links==
 +
:[[:Category:Viral Organisms|Viruses A to Z]]
 +
:[[:Category:Bacterial Organisms|Bacteria A to Z]]
  
*[[Clinical Case 3|Myxomatosis Clinical Case]]
+
==References==
 
 
*[[Poxviruses#Leporipoxviruses|The Myxomatosis Virus]]
 
 
 
*[[Viruses|Viruses A to Z]]
 
  
==Creators==
+
'''Textbooks'''
 +
*Ivan Roitt: '''Essential Immunology,''' Ninth edition
  
[[Natalie Brown]]
+
'''Lecture Notes'''
 +
*Dr Brian Catchpole BVetMed PhD MRCVS
 +
*Dr Peter H Russell BVSc MSc PhD MRCVS FRCPath
  
<big><center>[[Immunology - WikiBlood|'''BACK TO IMMUNOLOGY''']]</center></big>
+
<br><br>
<big><center>[[Host invasion by microorganisms - WikiBlood|'''BACK TO HOST INVASION BY MICROORGANISMS''']]</center></big>
+
{{Jim Bee 2007}}
 +
[[Category:Immunology]]

Latest revision as of 17:02, 4 June 2016

Syringe

Source: Wikimedia Commons; Author: ZaldyImg (2008)

Introduction

Why do we vaccinate animals?

  • 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.

How do vaccines work?

Vaccination induces an immunological memory of the infectious organism. High levels of cytotoxic T cells and neutralising antibody are activated 24 - 48 hours post vaccination as a secondary response (instead of 4-10 days later as a primary response). Neutralising 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 MHC class I processing live virus, recombinant virus or 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. This involves MHC class II processing inactivated and subunit vaccines.

Route of Administration

  • Usually by subcutaneous injection for systemic protection. Some vaccines such as the 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 (IgA) e.g. kennel cough vaccine.

Vaccination Options

Passive Immunisation - Copyright nabrown RVC

Passive immunisation

Advantages

  • Immediate protection

Disadvantages:

  • Short duration of action; temporary protection is obtained 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 over time
  • 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 when there is a failure of passive transfer of Immunoglobulin G
  • Antiserum
    • The antibodies are used in combination with antigen (and often an adjuvant) which is injected into a host animal
    • The immune system of that animal synthesises antibodies
    • Repeated injections at intervals increases 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


Examples of passive immunisation:

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 virus



Active Immunisation - Copyright nabrown RVC

Active immunisation

Active immunisation requires the administration of antigen so the patient develops their own antibodies to protect against disease. Suitable antigens include:

  • 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

Disadvantages

  • The host's immune system needs to evoke an immune response against the antigen which can take a few days
  • 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.

Vaccine Antigens

Potential antigenic substances include:

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.


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:

  • 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 prime the immune system initially, and then induce an immunoligical memory of the disease causing organism.

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).

Subunits (part of the organism)

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).

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.

Adjuvants

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 cell priming.

Different subtypes of T helper cells are stimulated by different adjuvants, for example:

  • Aluminium salts generate bias T helper II responses for antibody-mediated immunity
  • Killed mycobacteria generate IL-12 producing good cell-mediated immunity

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.

Marker Vaccines

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

  • 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

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 for the extracellular phase requires neutralising antibody:

Immunity for the intracellular phase requires CD8+ cytotoxic T lymphocytes (CTL) and uses the MHC class I pathway.

  • Only live vaccine can be used to get into cells (entering via the endogenous pathway)

Immunity to Bacterial Infection

Vesicular infections can only be cured by organisms being destroyed inside macrophages

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
  • Breeding females can be vaccinated so that immunity is passively transferred to their offspring via the colostrum - this 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.
  • Two vaccines are usually given to allow for differences between individual animals in the time taken for any natural immunity to decrease.

Dog Vaccinations

Diseases routinely covered by vaccination include:

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).

Cat Vaccinations

Cat - Copyright nabrown RVC

Diseases covered by Vaccination

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).

Rabbit Vaccinations

Rabbit - Copywright L. Drew RVC

Diseases covered by Vaccination

When to Vaccinate Rabbits can be vaccinated against 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 partially intradermally.

Vaccine Failure

Failures do occur and should be reported on the VMD '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 EU reporting forms for veterinarians which are available in each EU language on the 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.
  • Break down of the cold-chain during transport (incorrect storage of vaccines requiring refrigeration)
  • Improper administration (e.g.myxomatosis vaccine)
  • Accidental mixing of inactivated and live vaccines in the same syringe
  • Recipient has maternal antibody to the vaccine
  • Immunity waning due to missed booster vaccination
  • Vaccine is damaged during manufacture


Vaccines Learning Resources
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Full Text Articles
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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.

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

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.

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

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

Viruses A to Z
Bacteria A to Z

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



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