Immunology: Vaccines Flashcards
Ho are animals immunised passively against tetanus?
Donor animals hyper-immunised against specific pathogen
Serum collected or Ig purified
Administered to deficient animal e.g. im or iv (more rare)
Horse & sheep commonly used
How do we cause active immunisation?
Immunisation with vaccine antigen (usually against an infectious pathogen)
Commonly with adjuvants
Induces long-term (protective) immunity
Memory cells formed
What are the pros and cons of mucosal vaccination?
Local to site of pathogen invasion
May be the best as many pathogens enter the body via mucosal route
Immunity generally short-lived (weeks) – frequent boosters
How do adjuvants work?
enabling slow-release of vaccine antigens into the body to enhance immune recognition and response
OR stimulating the immune system non-specifically
Give some examples of adjuvants
– Aluminium and calcium salts (very safe; alum)
– Microbial products (bacterial cell wall extracts / fragments; “Freunds”)
– Synthetic agents (Carbopol, Immune stimulating complexes ISCOMs)
– Exogenous cytokines (e.g. IL-2 in tetanus vaccines)
Extracellular virus or bacteria are bound by neutralising antibody, preventing further infection and removal by effector mechanism, what are these mechanisms/
Effector mechanisms include opsonisation, phagocytosis, ADCC
Intracellular virus or bacteria which infect host cells are lysed by cytotoxic T lymphocytes (CTLs), can CTL’s kill extracellular virus?
CTLs do not kill extracellular virus
If a pathogen is intracellular and cytopathic, then lysis results in release of potentially infectious pathogens Hence….
Ab response is important in lytic viruses. In contrast if pathogen is largely intra cellular and spreads by intercellular dissemination (ie no extracellular phase) then CMI is more important and Ab less so.
How are live vaccines attenuated?
Mutants selected in vitro to reduce virulence but retain antigenicity (viruses and bacteria)
Mutants identified and selected from natural (field) strains
Deletion mutants - genetically modified to remove a gene*
Live “vectored vaccines” into which are inserted specific gene products
What are the advantages and disadvantages of live vaccines?
Advantage: CMI & Ab responses
Disadvantage: potential reversion to virulence
What is DIVA potential and why is it useful?
Genetic modification of the virus to remove a gene (gene deletion mutant) means that the animal will make an immune response to the virus but not to that gene product. As a result it’s possible to DIFFERENTIATE INFECTED FROM VACCINATED ANIMALS (DIVA) which is very desirable in managing an outbreak or exporting live animals
What makes reversion more likely when you vaccinate an animal?
With any live attenuated vaccine there is a danger of reversion to virulence. The risk of this is dependent on how easily the pathogen can either mutate or recombine with a wild type pathogen which happens to be present. Thus if the animal happens to be vaccinated at the same time as an active (subclinical) infection is occurring, there is a potential for recombination, acquisition of genes which cause virulence and thus reversion to a virulent form of the disease (which defeats the object of the vaccination!).
How to live vaccines work?
Vaccines infect host cells to a limited degree
Endogenous processing of antigens & presentation by APC in vivo via MHC class II
Infection of target cells and presentation by MHC Class I in vivo follows
Results in CTL recognition of virus & memory cells established (Th1 helper responses to enhance CTL activity & memory cells established)
Humoral immunity is also generated but less efficiently
Re-exposure of the vaccinated host to the pathogen results in anamnestic response
What are Live vectored vaccines (recombinant organisms)?
Pox viruses (Adenovirus, Vaccinia virus, Canarypox) are used as a backbone
Selected gene which encodes a protein associated with protective immunity is inserted.
E.g. Canopox + haemagglutinin gene of equine influenza virus
How do Live vectored vaccines (recombinant organisms) work?
• Result in low level infection and replication but without significant tissue pathology or clinical disease. Attenuate can occur by heating, chemical treatment or growing pathogen in unusual conditions e.g. low temperature
What are inactivated vaccines?
Killed whole or part organisms (inactivated virus or bacteria)
Unable to replicate so no clinical disease
Retain a degree of antigenicity
What are the advantages and disadvantages of inactivated vaccines?
Benefit: no danger of reversion to virulence
Disadvantages: only structural proteins are presented so need an adjuvant
How do inactivated vaccines work?
Inactivated organisms (whole virus/bacteria) are taken up by APC and the proteins / polypeptides processed exogenously Exogenous antigen processing & presentation by MHC Class II follows.
Results in:
– Th2 helper responses & cytokines to enhance differentiation of B cells into plasma cells (specific Ab secreted)
– Memory cells established
Cell mediated immunity (CTL) is also generated but less efficiently
Re-exposure of the vaccinated host to the pathogen results in anamnestic response
What are subunit vaccines
Inactivated vaccines
They need an adjuvant and immune response is restricted to the immunising antigen. This is fine if it’s been identified as a correlate of protective immunity. If not, then the immunity is very restricted.
What are two new types of vaccines on the market?
Naked DNA & recombinant organisms
• Stimulate both Ab & CMI responses
• Effective even in the presence of maternal Ab
FeLV: Needle free technology, high pressure, transdermal
What are the advantages of using a live vaccine vs inactive?
Table in notes
Why is vaccination for classica swine fever not done in the Uk?
Because we can’t tell the difference between a vaccinated animal or unvaccinated so it is a notifiable disease in the UK.
Vaccination against foot-and-mouth disease has also been stopped for a similar reason
What are the causes of ineffective vaccination in neonatal and aged animals?
Neonatal mammals:
– immunologically naïve (lack Ag exposure)
– immature immune systems (e.g. inefficient T cell production of IFNg)
– colostral antibody interferes with vaccine response until waned
Aged animals:
– often show immune senescence or compromised immunity.
– e.g. old horses (>15y) respond poorly to EIV vaccination. Experimentally, use of exogenous IL-2 enhances Ab responses to tetanus vaccines in old animals and people
