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→Vaccine Failure
Why do we vaccinate animals?
Why do we vaccinate animals?
*To protect against infectious diseases
*To protect against infectious diseases
*Where there is no effective treatment once infected E.g. [[Immunodeficiencies - WikiBlood#Feline Leukaemia Virus (FeLV)|FeLV]], FIV
*Where there is no effective treatment once infected e.g. FeLV, FIV
*Where disease is life-threatening E.g. Canine Parvovirus
*Where disease is life-threatening e.g. Canine Parvovirus
*To prevent the spread of disease by virus excretion E.g. Rabies, FMDV
*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
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|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.
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.
'''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.
==Route of Administration==
==Route of Administration==
*Usually by subcutaneous injection for '''systemic''' protection ([[Immunoglobulin G|IgG]]). Some vaccines such as the [[Myxomatosis|myxomatosis]] vaccine NobivacTM Myxo (Intervet UK Ltd) require an intradermal injection as part of the administration procedure.
*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.
*For a localised '''mucosal''' immune response, intranasal administration is required ([[Immunoglobulin A|IgA]]) e.g. kennel cough vaccine.
'''Disadvantages:'''
'''Disadvantages:'''
*Short duration of action; temporary protection is obtained by the administration of preformed [[Immunoglobulins|antibody]] from another individual of the same or of a different species. The acquired [[Immunoglobulins|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; 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]]
*Injection of antiserum may cause an [[Adverse Drug Reactions|allergic response]]
*Antiserum contains many [[Immunoglobulins|antibodies]], not just the specific [[Immunoglobulins|antibodies]] needed
*Antiserum contains many antibodies, not just the specific [[Immunoglobulins|antibodies]] needed
'''Types of [[Immunoglobulins|antibodies]] administered:'''
'''Types of antibodies administered:'''
*Maternally-derived [[Immunoglobulins|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]]
*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
*Antiserum
**The [[Immunoglobulins|antibodies]] are used in combination with Antigen Recognition|antigen (and often an [[Vaccines#Adjuvants|adjuvant]]) which is injected into a host animal
**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 [[Immunoglobulins|antibodies]]
**The immune system of that animal synthesises antibodies
**Repeated injections at intervals increases total [[Immunoglobulins|antibody]] production
**Repeated injections at intervals increases total [[Immunoglobulins - Overview|antibody]] production
**The immunised animal is bled and the serum collected which contains the newly made [[Immunoglobulins|antibodies]]. The serum is called '''antiserum'''.
**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
**The serum can then be injected into a different animal to confer passive immunisation
Examples of passive immunisation:
{| style="width:60%; height:200px" border="1" align=left
{| style="width:60%; height:200px" border="1" align=left
!INFECTION
!INFECTION
<br>
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[[Image:Active Immunisation.jpg|thumb|right|200px|Active Immunisation - Copyright nabrown RVC]]
[[Image:Active Immunisation.jpg|thumb|right|200px|Active Immunisation - Copyright nabrown RVC]]
===Active immunisation===
===Active immunisation===
Active immunisation requires the administration of antigen so the patient develops thier own [[Immunoglobulins|antibodies]] to protect against disease. Suitable antigens include:
Active immunisation requires the administration of antigen so the patient develops their own antibodies to protect against disease. Suitable antigens include:
*Living organisms
*Living organisms
*Dead organisms
*Dead organisms
'''Advantages'''
'''Advantages'''
*Long duration of action; once [[Immunoglobulins|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 antibody is produced against the antigen, [[B cell differentiation#Memory cells|memory cells]] are formed which continue circulating in the body
'''Disadvantages'''
'''Disadvantages'''
*The host's immune system needs to evoke an immune response against the antigen which can take a few days
*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 [[Immunoglobulins|antibody]] production ceases after a few weeks, but the second and subsequent doses create [[B cell differentiation#Memory cells|memory cells]] which remain in the circulation for a much longer period of time
*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==
==Vaccine Antigens==
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:
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
*The current vaccine for tuberculosis (called BCG) contains an attenuated form of a mycobacteria
*Vaccines for Leishmaniasis
*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
*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 casuing 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.
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).
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).
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.
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 protein 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
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).
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 cells|T cell]] priming.
Different subtypes of [[T cell differentiation|T helper cells]] are stimulated by different adjuvants, for example:
**E.g. Pathogen-associated molecular patterns (PAMPs)
*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
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.
===Marker Vaccines===
==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===
[[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
*Have a deleted protein or gene
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
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)
===Immunity to Bacterial Infection===
===Immunity to Bacterial Infection===
*Extracellular bacterial infection needs [[Immunoglobulins|'''antibody''']] production for [[Complement#Opsonisation|opsonisation]] and to activate the [[Complement|complement pathways]]
*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
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
==When do we vaccinate?==
==When do we vaccinate?==
[[Image:Colostrum Intake.jpg|right|thumb|150px|Colostrum Intake - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
[[Image:Colostrum Intake.jpg|right|thumb|200px|Colostrum Intake - 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]]
[[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]]
*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.
*Breeding females so immunity is passed to offspring via the [[Materno-Fetal Immunity - Introduction#Passive transfer via colostrum|colostrum]]
*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.
*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.
*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
*Two vaccines are usually given to allow for differences between individual animals in the time taken for any natural immunity to decrease.
===Dog Vaccinations===
===Dog Vaccinations===
Diseases routinely covered by vaccination include:
*[[Canine Parvovirus]]
*Canine [[Parvoviridae|Parvovirus]]
*[[Canine Distemper Virus|Canine Distemper]]
*Canine Distemper
*[[Infectious Canine Hepatitis]]
*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]]
'''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).
===Cat Vaccinations===
===Cat Vaccinations===
[[Image:Sebby cat.jpg|thumb|right|150px|Cat - Copyright nabrown RVC]]
[[Image:Sebby cat.jpg|thumb|right|175px|Cat - Copyright nabrown RVC]]
'''Diseases covered by Vaccination'''
'''Diseases covered by Vaccination'''
*Feline Infectious Enteritis ([[Feline Panleucopenia]])
*Feline Infectious Enteritis ([[Feline Panleucopenia]])
*Feline Infectious Respiratory Disease 'Cat Flu'
*'Cat Flu', including Feline [[Feline Herpesvirus 1|Herpesvirus]] and [[Feline Calicivirus]]
*[[Immunodeficiencies - WikiBlood#Feline Leukaemia Virus (FeLV)|Feline Leukaemia virus]]
*[[Feline Leukaemia Virus]] (FeLV)
*[[Immunodeficiencies - WikiBlood#Feline Immunodeficiency Virus (FIV)|Feline Infectious Viraemia]]
*[[Feline Immunodeficiency Virus]]
* Feline chlamydiosis
* [[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).
===Rabbit Vaccinations===
===Rabbit Vaccinations===
[[Image:Buzz bunny.jpg|thumb|right|150px|Rabbit - Copywright L. Drew RVC]]
[[Image:Buzz bunny.jpg|thumb|right|200px|Rabbit - Copywright L. Drew RVC]]
'''Diseases covered by Vaccination'''
'''Diseases covered by Vaccination'''
*Viral Haemorrhagic Disease
*[[Vaccinations_for_Rabbits#VHD_Vaccination|Viral Haemorrhagic Disease]]
*Myxomatosis
*[[Vaccinations_for_Rabbits#Myxomatosis_Vaccination|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==
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.
*VHD 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)
*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
{{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.]
[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]
[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.]
[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]
[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]
==Test Yourself==
|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]]
==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>
{{Jim Bee 2007}}
[[Category:Immunology]]
[[Category:Immunology]]