3.3 Vaccines and vaccination Flashcards
Why do we vaccinate ?
To prevent infectious disease in the individual / herd where this has health and welfare implications
– Not a substitute for good biosecurity and husbandry practices
To improve economic benefits in production animals
– Reduce the impact of endemic infections in intensive livestock systems
POPULATION MEDICINE AND VETERINARY PUBLIC HEALTH reason?
- To prevent the spread of a pathogen in a population
- To eradicate infectious disease rom a population
Ex: Emerging diseases (Rabies, BTV8, FMDV)
Principles of vaccination:
- Expose the host to foreign antigens without causing disease
– Educate the immune system what pathogens look like, without causing an infection or side effects
Short/ medium term
Antibody persists to neutralise pathogen
(long term)
Memory lymphocytes quick to react
What structural antigens are present for neutralizing antibody?
Surface expressed (surface spike proteins)
Passive immunisation (antibodies);
- colostrum antibodies (natural)
- antiserum (artificial)
Active immunisation (antigen)
-Toxoids
- Modified-live organisms
- Killed organisms
- Subunit antigens
- Recombinant DNA/RNA
What do we vaccinate with?
- Passive immunisation (antibodies)
- Active immunisation (antigen)
Passive immunisation: Colostrum antibodies
- vaccinate mother
- mother makes antibodies that are transferred via colostrum
- Maternally-derived antibodies (MDA) transferred to offspring in colostrum
What age do vaccines begin in puppies?
6 weeks
LactovacTM / RotavecTM vaccines:
- Contain rotavirus, coronavirus and E. coli (K99) antigen
- Vaccinate cow 3-12 weeks before calving
- Calves fed on colostrum / milk will be protected from enteric infection
Passive immunisation Antiserum
- Tetanus antitoxin (= antibodies) derived from horses immunised against tetanus
- Inject antibodies (antiserum) into horse at risk of developing tetanus. Should give immediate protection
Which immunization is Immediate but short duration of protection
Passive immunization
Active immunisation:
- Vaccinate animal
- Animal makes immune response
- Animal’s own immunity protects against infection
Active immunisation (antigen): toxoid
Some bacteria (esp Clostridia spp) are pathogenic by virtue of the toxins they produce
C. tetani =
Tetanus
C. botulinum =
Botulism “Botox”
C. difficile =
enterotoxaemia / flesh-eatin’ bug
____ effectively prevent the harmful effects of the toxin in the body
Neutralizing antibodies
Toxoid:
Looks similar to toxin but doesn’t have harmful properties
Tetanus toxoid vaccine:
- Administer tetanus toxoid to horse
- Horse makes antibodies (IgG)
- Antibodies neutralize toxin if animal subsequently injuries and the wound gets contaminated with C. tetani
Killed (inactivated) vaccines:
- Virulent organisms cannot be used as vaccines as they would cause disease.
- The organism can be killed so that it no longer replicates, but still contains the antigens required to stimulate an immune response.
Killed (inactivated) vaccines: chemicals
- Formaldehyde - crosslinks proteins
- Alkylating agents - crosslinks nucleic acids
Killed (inactivated) vaccines: heat or radiation
Sterilizes organisms
Modified live (attenuated) vaccines:
- Virulent organisms cannot be used as vaccines as they would cause disease
- Their virulence can be reduced (attenuated) so that the organism is still alive but grows so slowly that it does not cause disease.
- low virulence mutant organisms identified to produce a ‘vaccine strain’
Attenuation
Grow virus in lab under unusual conditions to drive natural selection of low virulence mutants:
- Temperature sensitive mutants adapted to 35oC rather than 37oC
- Grow in unusual cell line so that adapted strain is less able to replicate in target host species.
Genetic modification
- targeted disruption of virulence genes
Responsible for attachment ?
Spike protein
Subunit vaccines: FeLV
- Leukocell 2 (Zoetis): Purified gp70 envelope protein from virus-infected cells
-Leukogen (Virbac): Recombinant (cloned) p45 envelope protein produced in E. coli
Recombinant vaccines identify?
Encoding antigen:
Clone encoding sequence into
- plasmid DNA
- virus vector
Recombinant vaccines: When injected into animal, recombinant protein is made in
vivo and stimulates an immune response
Recombinant virus vaccine for FeLV
PureVax FeLV (Merial):recombinant canarypox vaccine expressing FeLV gp70
• Canarypox can infect mammalian cells but cannot complete its life-cycle.
• Protein antigen is produced by viruses attempt to replicate.
• Protein antigen stimulates immune response.
Recombinant virus vaccine for Covid-19:
• Coronavirusspikeproteingeneidentified
• Cloned into a simian adenovirus
How does the Covid-19 vaccine work?
Adjuvants:
- Oily substances – act as a depot of antigen to allow longer exposure of the immune system
- Act like PAMPs to trigger innate immunity (viaPRRs) that influences adaptive immune responses
Adjuvants quantitative effect:
Added to killed and subunit vaccines to enhance their immunogenicity and increase antibody response
Adjuvants qualitative effect:
Can alter the antibody isotype produced
- IgG / IgA / IgE
Can alter the TH1 : TH2 balance influencing cell- mediated vs antibody-mediated response
How do we deliver vaccines ?
- Usually by subcutaneous (or intramuscular) injection for systemic protection (IgG usually)
- Intranasal administration for good mucosal immune responses (i.e. IgA rather than IgG)
e.g. Kennel cough vaccines
Problem with killed / subunit vaccines?
Single antigen = short antibody response, need another dose for replication
MLV / recombinant virus vaccines =
High titre and long plateau phase
Vaccine protocols: When vaccinating animals >12 weeks of age
- Killed / subunit vaccines generally require two doses given 2-4 weeks apart.
– MLV / recombinant virus vaccines might only require a single dose.
Vaccine protocols: when vaccinating young animals
- Immune system is immature up to 6 weeks of age
– Maternally-derived antibody (MDA) may interfere with vaccination up to 12 weeks of age
– Generally administer a primary course of two doses given at 8 weeks and 12 weeks of age
When are general boosters given?
one year after primary course
When are subsequent boosters given?
Every 1-3 years
– Many modern MLV have a 3 year “duration of immunity”
Ex: rabies DA2PPL
What happens if booster is missed?
No immunological reason to ‘start the primary course again’ if a booster is missed
– Memory lymphocytes are still there
– But this might be a regulatory requirement
(e.g. FEI regulations on equine influenza vaccination)
How do we know that the vaccine has worked ?
- The owner gets a signed vaccination certificate
• Should perform serology post-vaccination but this is not commonly done in general practice
• Some evidence that certain breeds (e.g. Rottweiler and Dobermann) have a higher prevalence of vaccine failures
Pet Travel Scheme (PETS):
- Rabies serology is recommended as part of PETS (NB change in EU regulations from Jan 2012)
- Blood test 3-6 weeks post-vaccination
- Must reach >0.5 IU/ml on FAVN test in order to be considered ‘test positive’
Reasons for vaccine failure:
- The vaccine does not contain appropriate antigens for the strain/serotype of pathogen to which the host is exposed (e.g. Influenza, Leptospirosis)
- the vaccine has not been stored properly
- has not been administered properly
Reasons for vaccine failure (host factors)
-Age
- prior exposure to pathogen (persistent infection ( herpes / retrovirus)
- animal is immunocompromised in some way (chronic disease, concurrent infection, chemotherapy)
- genetically programmed to generate an inappropriate response
Reasons for vaccine failure (host factors): Age
– Not immunocompetent (<6w YOUNG)
– Interference from MDA (6-12w)
– Immunosenescence (“old age”)
Vaccine adverse effects: Feline injection site sarcoma
- Cats vaccinated against FeLV/rabies
- Annual exposure of the tissues to a mutagenic adjuvant
– Use a non-adjuvanted vaccine (PureVax FeLV, Merial)
– Rotate sites of administration
Therapeutic vaccines stimulate?
- immune response against tumour antigens: anti-cancer vaccines
- Human tyrosinase DNA vaccine available for treatment of canine malignant melanoma
Some canine vaccines are recommended to be given to puppies at 8 and 10 weeks of age… why?
allows early socialization (daycare, parks) …but more vaccine failures
