Introduction to Veterinary Vaccines Flashcards
Adaptive Acquired Immunity
Two Approaches: 1. Humoral / Antibodies 2. Cell Mediated Need to recognise two distinctly different forms of foreign invaders Both aided by T helper cells
Extra-Cellular
Humoral / antibodies B Cell
Inside Cells
Cell mediated immunity Tc cells
The direction of the Th cell response governs
the nature of the immune response. Th1 promotes CMI, Th2 promotes humoral responses.
Serum antibody titre conferred by passive immunisation
Administration of antibodies from a resistant animal to a susceptible animal
Gives immediate protection but as the antibodies are broken down, the immunity diminishes
Artificial Passive Immunisation
Donor animal repeatedly immunised against antigen, then bleed. As Ab levels decrease, repeat immunisation.
Used against anthrax in cattle
distemper in dogs
panleukopenia in cats
measles in humans
Most important one raise is against Clostridium tetani and C. perfringens where Abs raised in horses
Only gives relatively short protection
Problems with Passive Immunisation
Maternal antibodies may interfere with active immune response
Do not administer pulpy kidney vaccine to lambs from vaccinated ewes until ~6-8 weeks of age
As seen in the dog, serum antibody levels will decrease quickly as regarded as foreign!
reduce response for heterologous species by pepsin treatment
However, if circulating antibodies present once the animal has mounted an immune response it can cause
Immune complex formation (type III hypersensitivity reaction called serum sickness)
If repeated dose of horse antibodies are give it may provoke IgE production and anaphylaxis!
Central features of Active Immunisation
Administration of antigen to an animal so that it responds by mounting a protective immune response
Reimmunisation or exposure to infection will provoke a secondary response
Protection is not immediate
Active Immunisation
Provides prolonged period of protection that can be boosted by repeated injection of antigen or infection
However, they must
Stimulate APC to produce appropriate cytokines
Stimulate both T and B cells
Stimulate T helper cells to sufficient epitopes to overcome MHC class II polymorphism
Must persist in appropriate sites in lymphoid tissue so that Ab production will last as long as possible
Must be safe!
Many potential vaccine failures are due to not meeting one or more of these requirements!
Antibodies in immunity against viruses
Antibodies can bind to free viruses to prevent them from entering cells (neutralisation).
Once antibody binds virus infection will not occur
virolysis
Virus in blood can be destroyed by antibodies binding to them
Virus in blood can be destroyed by antibody binding and aiding
phagocytosis by neutrophils
Factors affecting immune responses to vaccines
- Genetics: (not much can be done apart from selection)
- Age: mature animals generally respond better than young. May be due to an immature immune system or passively acquire IgG
Health: Pre-existing disease may decrease response to Ag
Nutrition: Undernutrition or deficiency reduce both IgG and CMI responses
Stress: Although considered to be suppressive, can alter Th balance towards a Th2 response
- Incorporation of Adjuvants: Compounds that provoke a stronger immune response eg. Alum (aluminium hydroxide) provides a slow release mechanism for antigen triggering a stronger response
If a live viral vaccine is used…
it will replicate within a cell. The infected cell will then process the endogenous antigen
stimulates CD8+ cells
However, early killed / inactivated vaccines acted as exogenous antigen
stimulates CD4+ cells
Attenuated / Living Vaccines
Virulent living organisms CANNOT normally be used !
Virulence must be reduced so that it still living but can no longer cause disease
Usually attenuated by prolonged tissue culture in non- host cells
Canine distemper virus usually infects lymphoid cells
repeated culture in canine kidney cells virulence is lost
Difficult to distinguish between infected and vaccinated animals based on serology!
Some animals more susceptible to live vaccines eg Afghan hounds at risk of ‘blue eye’ after CAV 1 canine hepatitis vaccines than other breeds
Inactivated Vaccines
Killed
Can sometimes produce an effective vaccine by killing the pathogen
However, if not careful may get protein denatured and lipid oxidation (not good!)
Chemicals such as formaldehyde also act on protein and nucleic acid to form cross-links and confer structural rigidity
Also possible to treat toxoids with formaldehyde to stimulate neutralising antibodies (tetanus)
M. haemolytica contains both killed bacteria and inactivated bacterial leukotoxin
Live Vaccines
Few inoculations required Less chance of hypersensitivity Induction of interferon Relatively cheap Use of antimicrobial reduced effect May cause abortion / concurrent infections
Inactivated Vaccines
Stable on storage
Adjuvants required
Unlikely to cause disease through residual virulence
Unlikely to contain contaminating organisms
Safe to use during pregnancy
Possible to produce effective new vaccines by genetic engineering and recombinant DNA technology
Four categories
I Contain inactivated recombinant organisms or purified antigens derived from recombinant organisms.
II Contain live organisms that contain gene deletion or heterologous marker genes.
III Contain live expression vectors containing heterologous genes for immunising antigens or other immune stimulant.
IV Genetically engineered vaccines comprising of nucleic acids
Antigens Generated by Genetic Engineering
Category I
Require to identify main antigens and isolate DNA / RNA coding for this antigen
If RNA genome virus, convert to cDNA by reverse transcriptase
Insert this DNA into bacterium, yeast or other cell. Culture and isolate antigen
Mix with adjuvant to give subunit vaccine
Effective FeLV vaccine was first veterinary subunit vaccine (recombinant gp70 and p15e proteins)
Also recombinant OspA used to control Lyme disease (Borrelia burgdorferi)
Alum
very effective at triggering TH2 phenotypes and humoral responses
Genetic Attenuated Organisms
Category II
A laboratory method of speeding up attenuation!
Try to mutate / remove a gene vital or virulance
Thymidine kinase (TK) is required by herperviruses to replicate in nondividing cells, such as neurons
By removing TK gene, virus is able to infect cell but cannot replicate and cause disease
Live Recombinant Organisms
Category III
Require to identify main antigens and isolate DNA / RNA coding for this antigen
Insert this DNA a non pathogenic organisms and use a vaccine
Examples include
Rabies vaccine where G protein (rabies envelope glycoprotein) inserted into vaccinia
effectively used in Belgium
Also used against rinderpest, and Newcastle disease vitus
Nucleic Acid Vaccines
Category IV
This vaccination method involves injection of a piece of purified DNA for the specific antigen, not the protein!
Target DNA is cloned into an E. coli delivered plasmid
Target vaccine gene is place under the control of a strong mammalian promoter sequence
Injected intramuscularly and taken up and expressed in host cells
Very good at promoting a Th1 response
applied experimentally (so far) to produce vaccines against bovine viral diarrhoea, feline immunodeficiency virus, canine and feline rabies
Adjuvants
Adjuvants are used in vaccine formulations to induce potent immune responses that cannot be obtained with antigen alone.
Gaston Ramon (1886-1963) – antisera production increased from horses that developed abscess at site of injection
Later induced inflammation (eg starch) to increase Ig production
Alexander Glenny (1882-1965) demonstrated primary and secondary immune responses and the enhancing effects of aluminium salts (alum) After approval, alum was the sole adjuvant in vaccines for 70 years
Depot Adjuvants
Aluminium phosphate (or hydroxyde
Alum
Slow release antigen depot
Activate DAMPs
Emulsions
Oil-in-water emulsion (eg Freund’s)
Slow release antigen depot plus immune stimulant
Microbial adjuvants
Bacteria-derived immunostimulant
Macrophage or Lymphocyte stimulant
Immune Stimulators
Saponin Glucans IL18 (DNA vaccines) Flagelin Stimulate macrophage and/or antigen presenting cells
Delivery Systems
ISCOMS
Liposomes
Nanoparticles
Stimulates antigen presenting cells
Herd Immunity
The concept is not new and can be used to define different concepts:
Proportion immune among individual in a population
A threshold proportion of immune individuals that should lead to a decline in incidence of infection
A pattern of immunity that should protect a population from invasion of a new infection
“the risk of infection among susceptible individuals in a population is reduced by the presence and proximity of immune individuals”
Basic Reproduction Number
R0
Number of secondary cases generated by a typical infected animal when the population is susceptible
Critical vaccination level
Vc
Proportion of the population that must be vaccinated to achieve herd immunity threshold
Vaccine effectiveness against transmission
E
Reduced transmission of infection to and from vaccinated animals compared with nonvaccinated animals
