Immunology: Vaccines

Question 1

Ho are animals immunised passively against tetanus?

Answer 1

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

Question 2

How do we cause active immunisation?

Answer 2

Immunisation with vaccine antigen (usually against an infectious pathogen)
Commonly with adjuvants
Induces long-term (protective) immunity
Memory cells formed

Question 3

What are the pros and cons of mucosal vaccination?

Answer 3

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

Question 4

How do adjuvants work?

Answer 4

enabling slow-release of vaccine antigens into the body to enhance immune recognition and response
OR stimulating the immune system non-specifically

Question 5

Give some examples of adjuvants

Answer 5

– 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)

Question 6

Extracellular virus or bacteria are bound by neutralising antibody, preventing further infection and removal by effector mechanism, what are these mechanisms/

Answer 6

Effector mechanisms include opsonisation, phagocytosis, ADCC

Question 7

Intracellular virus or bacteria which infect host cells are lysed by cytotoxic T lymphocytes (CTLs), can CTL’s kill extracellular virus?

Answer 7

CTLs do not kill extracellular virus

Question 8

If a pathogen is intracellular and cytopathic, then lysis results in release of potentially infectious pathogens Hence….

Answer 8

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.

Question 9

How are live vaccines attenuated?

Answer 9

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

Question 10

What are the advantages and disadvantages of live vaccines?

Answer 10

Advantage: CMI & Ab responses
Disadvantage: potential reversion to virulence

Question 11

What is DIVA potential and why is it useful?

Answer 11

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

Question 12

What makes reversion more likely when you vaccinate an animal?

Answer 12

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!).

Question 13

How to live vaccines work?

Answer 13

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

Question 14

What are Live vectored vaccines (recombinant organisms)?

Answer 14

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

Question 15

How do Live vectored vaccines (recombinant organisms) work?

Answer 15

• 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

Question 16

What are inactivated vaccines?

Answer 16

Killed whole or part organisms (inactivated virus or bacteria)
Unable to replicate so no clinical disease
Retain a degree of antigenicity

Question 17

What are the advantages and disadvantages of inactivated vaccines?

Answer 17

Benefit: no danger of reversion to virulence
Disadvantages: only structural proteins are presented so need an adjuvant

Question 18

How do inactivated vaccines work?

Answer 18

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

Question 19

What are subunit vaccines

Answer 19

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.

Question 20

What are two new types of vaccines on the market?

Answer 20

Naked DNA & recombinant organisms
• Stimulate both Ab & CMI responses
• Effective even in the presence of maternal Ab

FeLV: Needle free technology, high pressure, transdermal

Question 21

What are the advantages of using a live vaccine vs inactive?

Answer 21

Table in notes

Question 22

Why is vaccination for classica swine fever not done in the Uk?

Answer 22

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

Question 23

What are the causes of ineffective vaccination in neonatal and aged animals?

Answer 23

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