Vaccination

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Vaccination

• Lab 14

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Immunity

• Active immunity
• Develops as a result of infection with a
  microorganism
• OR administration of vaccine prepared from live
  or inactivated organisms, antigenic fractions or
  detoxified exotoxins

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Immunity

• Passive immunity
• Transfer of maternal antibodies to offspring or
  injection of antibodies
• Domestic Mammals intestinal absorption of
  antibodies from colostrum within 1st few hours of
  life
• Birds maternal antibody transferred to yolk
  where developing chick absorbs it
• No maternally derived passive immunity in fish

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Vaccines

• Preparations of antigenic material
• Administered to induce active immunity in
  recipient animal against a specific organism
• Vaccines may be single component or mixed
  combined preparations
• Immune response usually specific for each agent
  although cross protection may occur

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Why vaccinate?

• prevent/reduce severity of disease in individual
  
• animals/herd
• Limit pathogen spread within populations
• reduce suffering/death in companion animals
• improve welfare/reduce losses in production
  animals due to disease
• e.g. improved growth rates, improved milk
  yields, improved fecundity
• reduce transmission of zoonotic or food borne
  diseases
• protection of endangered species/animal
  collections
• aid eradication programmes e.g rinderpest FMDV

• Cost effective
• Cheap
• Efficient prevention
• Profit for veterinarian

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The perfect vaccine is?
Safe
Efficacious (induces protective immunity in all
vaccinated animals)
Evokes long lasting immunity
Minimal requirement for boosting
Stable and easy to administer
Commercial considerations
- Cost, compatibility with other vaccine
components, etc
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In Practice

• Who do I vaccinate ?
• mother (for passive immunity in young),
  susceptible

• Should I vaccinate ? (Must I vaccinate?)
• animal health, pregnancy status, timing,
  risk
• Which vaccine do I use ?
• manufacturer, efficacy, components......
• When do I administer and how often
• safety, boosting intervals (gt annual ?)
• How do I administer (and store)
• preparation, route, site

Literature
Manufacturers datasheet
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Current vaccines

• Inactivated vaccines
• Live vaccines
• Single component
• Multi component
• Passive protection (antisera)

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Inactivated Vaccines

• Most commonly used at present
• Whole virus or bacterial cells
• Known as BACTERINS if bacterial
• Formaldehyde inactivated
• Preserved with phenol
• Mixed with adjuvant

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Antigens preserved in inactivated vaccines

• Envelope (viruses)
• Fimbriae
• Capsules
• Outer membrane proteins
• Cell wall lipopolysaccharides
• Iron binding proteins
• Toxins

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Production of Inactivated Vaccines

• Seed stock maintained at low passage to conserve
  pathogenic determinants
• Grow culture to produce optimum yield of
  pathogenic determinants
• Harvest cells or precipitate supernatant
• Inactivate toxins to toxoids
• Add adjuvants and preservative
• Pack for distribution
• Normally require more than one administration

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Inactivated (killed) vaccines
Whole Cell/Culture Kavak L,
Fort Dodge, Merthiolate-killed Leptospira
icterohaemorrhagiae and L. canicola for
dogs Capsules
Suvaxyn APP, Fort dodge, killed
whole cell vaccine with capsular antigens from
serotypes 3,6, and 8 of Actinobacillus
pleuropneumoniae for pigs Cell
membranes Stellamune, Pfizer, Mycoplasma
hyopneumoniae killed culture vaccine for enzootic
pneumonia in pigs Fimbriae Porcilis Porcol 5,
Intervet, K88ab, K88ac (F4), K99 (F5) 987P (F6)
and LT Toxoid of E. coli against piglet
diarrhoea Crude culture supernatant
Blackleg vaccine BP (Vet), Schering Plough,
Whole culture inactivated Clostridium chauvoei
With toxoids. Vaccine for cattle Iron
restricted proteins Salenvac, Intervet

• Contain sufficient antigen to stimulate antibody
  production
• Generally require 2 doses in order to generate
  sufficient response for protection
• Inactivation may modify surface antigens
• Organisms are dead so wont replicate
• May be whole killed bacteria or bacterial
  components known as sub-units
• Given by injection
• Annual boosters

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Use of Inactivated Vaccines

• Intramuscular parenteral administration
• Two or more injections
• Elicit IgM and IgG antibodies
• Poor local (mucosal) and cellular immunity
• Poor duration of immunity
• Passive immunity for offspring
• (vaccinate mum)

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Disadvantages of killed vaccines
1. Need to ensure complete inactivation
2. Cellular components may cause side
effects Rabies vaccine produced in neural tissue
(Semple-type vaccines) can cause neurological
problems in human beings (now superseded)
FMD vaccine produced in tissue culture can cause
hypersensitivity and anaphylaxis in cattle
3. More than one injection usually required
4. Cold chain required for storage and transport
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Component Vaccines

• One or more protective antigens
• Toxoid, secreted antigen and/or structural
  proteins
• Require moderate amounts of antigen
• Administered with adjuvant

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Toxoids

• Toxins obtained from bacteria (supernatant,
  secreted) and treated by heat or chemicals
  (formaldehyde)
• Destroys toxicity and capability of causing
  disease but retains immunogenicity
• Stimulate the formation of toxin neutralising
  antibodies
• Usually contain adjuvants

Toxins
Lambivac, Intervet, Lamb Dysentery, Struck,
Pulpy kidney and tetanus vaccine for sheep, -
TOXOIDS of C. perfringens Types B, C and D and C.
tetani with alum and thiomersal preservative
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Adjuvants

• Inactivated vaccines contain adjuvants that
  enhance the immune response to the vaccine
• Induce inflammation at the site of vaccination
• May cause local irritation and swelling at site
  of vaccination
• Adjuvants used are aluminium hydroxide, aluminium
  phosphate, alum, mineral oil such as liquid
  paraffin

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Adjuvants that enhance immune responses
Name Composition Mechanism of action
Freunds incomplete Oil in water emulsion Delayed release of antigen enhanced uptake by APC
Freunds complete Oil in water emulsion killed mycobacteria As above but also activates macrophages
Alum (aluminium hydroxide) Aluminium hydroxide gel Delayed antigen release, enhanced uptake
ISCOMS (immune stimulating complexes, saponin isolated from Quillaja Saponaria mixed with cholesterol and phospholipid. Matrix of lipid micelles containing protein Enhanced antigen uptake, delivers antigen to cytosol, Th cell and CTL induction.
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Live Vaccines

• Live microorganisms that have lost ability to
  cause disease by treatment with
• - sublethal chemicals
• - multiple passage on lab media
• - passage in cells
• - through a different host
• - heat
• Non pathogenic forms of the infecting organism
• Retain many or all of the surface antigens from
  which they are derived
• Replicate in the host but cause no disease
• Stimulate CMI and antibody both locally and
  systemically
• Not genetically defined

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Live Vaccines
Bordetella bronchiseptica, Attenuated strain,
INTRANASAL FOR KENNEL COUGH (Intrac, Schering
Plough) Bacillus anthracis, Capsule deleted,
INTRAMUSCULAR FOR CATTLE (Anthrax spore vaccine,
DEFRA, Licence only) Chlamydophila abortus,
Freeze dried attenuated strain 1B, intramuscular
for ENZOOTIC ABORTION IN SHEEP (Tecvax Chlamydia,
Vetoquinol) Salmonella enteritidis,
Naturally-attenuated oral vaccine for poultry
(Lohmann) Trichophyton verrucosum, Attenuated
live freeze dried vaccine given intramuscularly
FOR RINGWORM IN CATTLE (Ringvac Bovis LTF-130,
Intervet)

• Live vaccines stimulate immunity at mucosal
  surfaces, the entry points for most pathogens (GI
  tract, Respiratory tract)
• Living vaccines colonise and replicate on the
  surface of appropriate mucosa
• Immunity long lasting usually but generally less
  than that following natural infection
• Maternal antibody and antibiotic treatment may
  inhibit vaccine replication

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Disadvantages of live-attenuated vaccines
1. Possible presence of adventitious agents in
the cells and medium used for growth 2.
Cold chain required for storage and transport
3. Limited shelf-life 4. Reversion to
virulence / side effects
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Passive immunity

• Provided by dam
• Requires first administration and boost
• Booster given before parturition
• Egg/placental transmission in some species
• Colostral antibody in most farm species
• Milk antibody

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Veterinary immunotherapy and prophylaxis

• Hyperimmune polyvalent antisera used
  traditionally
• Raised in horses
• Monoclonals now available
• Colostrum/immunoglobulin from other species
• Given before disease/after exposure

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Current Hyperimmune Antisera
Tetanus Antitoxin Behring, (Intervet), 1000 units
antitoxin/ml derived from horses and preserved
using 0.5 phenol, subcutaneous or
intramuscular Lambisan, (Intervet), Lamb
dysentery, struck and pulpy kidney, Antiserum
raised in horses to C. perfringens ? and ?
toxoids given subcutaneously

• Commercially available preparations of antisera
  produced by immunising horses or cattle
• Sera contain the appropriate antibodies or
  antitoxins
• Provide passive protection when unimmunised and
  exposed e.g. tetanus
• May produce hypersensitivity in recipient of sera

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What you need to know

• How specific diseases are controlled (is vaccine
  used?)
• Aim of vaccination
• Types of vaccine
• Limitations of vaccines
• Where to find detailed information as to HOW and
  WHEN to vaccinate

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Vaccine development emerging disease

• Are current vaccines available for related
  strains
• Do they protect against emerging strains ?
• If new vaccine required time lag
• development, safety and efficacy testing
• other potential limitations availability of
  reagents for production (eggs H5N1), effect of
  time lag re antigenicity in vaccine vs field
  strains, appropriate to use
• Importance of hygiene/husbandry/isolation
  measures
• until vaccine developed

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Why develop new vaccines?

• induction of more effective/longer lasting
  immunity
• (in more animals)
• induction of better immunity than wild type
  virus infection
• increased safety nonliving gtliving
• protection against currently circulating strains
  
• (new vaccine components/greater cross
  protection)
• development of vaccines against new/emerging
  diseases
• development of therapeutic vaccines

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Safety/efficacy issues
Quality control
- incomplete inactivation of 'inactivated
vaccine' - contamination of live vaccine with
another pathogen or reversion to virulence -
ineffective vaccine due to poor quality
control, inappropriate storage or administration
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Safety/efficacy issues
Biological

• - reaction to adjuvant
• - vaccine-associated sarcomas (cats)
• - autoimmune disease ? other long-term effects
• - immunosuppressed/pregnant animals and live
  vaccines
• interference from maternally derived antibody
  (MDA)
• variation in response to vaccination in different
  animals
• antigenic diversity/drift in field strains

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Summary
Vaccination is major means by which viral disease
is prevented
Immunisation - Passive (MDA, Ig, boosted MDA)
Active (pathogen/vaccination)
Non-living Living
Application of molecular techniques to produce
next generation vaccines