Unit 4c. Vaccination

Question 1

essentials of the Acquired Immune Response

Answer 1

the acquired immune system is equipped with B-cell receptors and T-cell receptors that specifically respond to an endless profile of microbial antigens during antigen presentation

this process of antigen recognition leads to an antigen specific B-cell and T-cell activation, which initiates an antibody mediated response (AbMIR) to destroy intracellular pathogens

Question 2

Immunological Memory

Answer 2

in addition to antigen recognition and pathogen killing, the acquired immune system also has the capacity for “memory” such that subsequent exposure to antigen elicits an enhanced and more efficient immune response
without this immune capacity it would not be possible to develop and use vaccines to enhance immunity to pathogens

Question 3

Factors influencing Antigen Immunogenicity

Answer 3

types of antigens: the most immunogenic antigens are proteins larger than 1000 DA in size

surveillance (sentinel) immune cells are well equipped to process proteins and present their antigenic peptides to T-cells via major histocompatibility complex (MHC) class I and II molecules

• MHC I will drive cell mediated response
• MHC II drive antibodies mediated response

Question 4

Antigen Processing and Presentation by MHC class I And II molecules

Answer 4

endogenous pathway: all host cells infected with an intracellular pathogen are capable of presenting endogenous antigenic peptides on MHC class I molecules to cytotoxic T-cell (Tc) 
 - if the TCR in the Tc recognizes the antigenic peptide, the T-cell becomes activated and sends a death signal to the infected host cell, which forces it to undergo programmed cell death

Question 5

Antigen Exposure Route

Answer 5

Antigen exposure route influences the type of immune response that is mounted during vaccination

Question 6

Genetics

Answer 6

mutations in genes coding for a microbial protein antigen will influence immunogenicity, and some pathogens under host selection pressure utilize this to evade the immune response

Question 7

EXAMPLE: Epitopes on Influenza virus- hemagglutinin antigen

Answer 7

the antigenic determinants of a protein are referred to as epitopes. since there are potentially many epitopes on a single protein, some being more immunogenic than others, an immune response will be mounted against each epitope with varying effectiveness: overtime the immune response will favour an immunodominant epitope

the challenge with vaccine development is to incorporate an antigen that possesses an immunodominant epitope in order to elicit an immune response that provides immunity against the target pathogen before exposure occurs

influenza virus is constantly changing these epitopes via gene mutations to evade the host immune response, and this is why influenza vaccines are not always highly effective from one flu season to the next

Question 8

Stability

Answer 8

increasing antigen stability increases immunogenicity

plant based vaccines for example, have been shown to increase antigen stability and immunogenicity because the plant cell wall protects the antigen as it passes through the acidic and enzyme rich gut to lymphoid tissue of the small intestine

Question 9

Foreignness

Answer 9

the more genetically dissimilar the antigen is from the vaccine recipient, the more immunogenic it will be

Question 10

complexity

Answer 10

the more complex an antigen is, the more immunogenic it will be
polysaccharides and lipids making up a microbial cell membrane are not very immunogenic, however, when they are conjugated to a protein, their immunogenicity is dramatically increased

Question 11

Dose

Answer 11

a low antigen does may not be sufficient to elicit an immune response, whereas a high antigen dose may be lethal or may shut down the immune system (anergy)

Question 12

examples of adjuvants

Answer 12

alum
calcium phosphate
freunds incomplete adjuvant - water-in-oil emulsion
monophosphoryl lip A from lipopolysaccharides
CpG oligonucleotides
cholera toxin
plant saponins

Question 13

Live Attenuated Vaccines

Answer 13

used most frequently for preventing viral infections, in order to provide immune protection against these intracellular pathogens, the vaccine must elicit a CMIR (cell mediated immune response)

vaccines containing live pathogen are most effective for eliciting CMIR because the antigen can be processed via the endogenous antigen processing pathways, which leads MHC class I antigen presentation to T-helper cells

the most common attenuation method involves passing the virus through succession of cell coulters under limited growing conditions to weaken it

Question 14

Advantages of live attenuated vaccines

Answer 14

fewer immunizations required to elicit longterm immunity
no requirement for an adjuvant
reduced risk for hypersensitivity reaction
induces antiviral interferon response
can be administered by natural route
provides long lasting immunity
elicits CMIR and ABMIR

Question 15

Shortcomings of live attenuated vaccines

Answer 15

possibility of mutation occurring that will increase virulence
may cause illness in immune compromised individuals

Question 16

Inactivated Vaccines

Answer 16

the pathogen is inactivated using heat, radiation or certain chemicals
antigens are processed by exogenous antigen processing which leads to MHC class II antigen presentation to T-helper cells, and subsequent elicitation of an acquired immune response

Question 17

Advantages of inactivated vaccines

Answer 17

longer shelf life
easier to store
less likely to cause disease or infection
no risk of pathogen increasing virulence

Question 18

Shortcomings of inactivated vaccines

Answer 18

does not always provide long term immunity, boosters may be needed
also possibility of hypersensitivity reaction

Question 19

Subunit vaccines

Answer 19

antigenic proteins are isolated from a pathogen and incorporated into a vaccine
immunization triggers an antigen-specific acquired immune response without causing infection
may need an adjuvant

Question 20

shortcomings of subunit vaccines

Answer 20

isolation of the antigenic protein is costly and time consuming
also it may not always provide the long-term immunity

Question 21

Vector-delivers subunit vaccines

Answer 21

the gene coding the antigenic protein from the pathogen can be instead in to a bioreactor and later purified for incision in a vaccine

the gene coding the antigen protein can be inserted into a vector, which is then delivered to the vaccine recipient

Question 22

Advantages of vector approach

Answer 22

1. it could replace costly and labour intensive parental antigen delivery strategies
2. it could alleviate the need for booster immunizations because the immune system is under constant stimulation with antigen
3. it could help stabilize antigen –> pass through the stomach before being broken down so it can be absorbed by SI

Question 23

Conjugate Vaccines

Answer 23

these vaccines contain poorly immunogenic but important bacterial membrane target antigens; immunogenicity can be increased by chemically linking these antigens to a carrier protein

Question 24

Toxoids

Answer 24

some bacteria release harmful toxins that cause illness in infected animals
toxoid vaccines contain antigenic toxins that have been chemically inactivated
immunization with the immunogenic toxoid induces an acquired immune response, without causing toxicity

Question 25

Active Immunization

Answer 25

a microbial antigen is administered to an animal in a vaccine to elicit an acquired immune response.
re-immunization with the antigen results in enhanced and long-lasting immunity provided by memory T- and B-cells that were generated during the primary immune response

Question 26

Passive Immunization

Answer 26

antigen-specific antibodies are trasnferred from a “resistant donor” animal to a “susceptible recipient” animal. this provides immediate but temporary immunity
passive immunization is most effective against toxin -producing organisms

Question 27

Adverse Immune Reaction to Passive Immunization

Answer 27

an adverse immune reaction can occur if the recipient animals immune system recognizes and mounts an immune response against the “non-self” donor antibodies

if donor antibodies are still present during the recipients immune response, it can cause serum sickness
if dose is repeated anaphylaxis can occur

both of these can be minimized by ensuring a single donor antibody treatment for a short duration of time

Question 28

Maternal- neonatal Passive Immunity

Answer 28

transfer of maternal antibodies to offspring via colostrum

ruminants and piglets rely very heavily on colostrum for passive immunity

Question 29

administrations of vaccine

Answer 29

most vaccine are administered by parenteral delivery (injection) and they elicit a systemic immune response
in the case of birds: aerosol, water or food is preferred
for fish, immersion and food is preferred

Question 30

Duration of Immunity

Answer 30

not all vaccines provide long-term immunity, it has bee common practice to administer an annual booster for these vaccines
an alternative is to measure serum antibody tigers by ELISA to determine if a booster immunization is required

Question 31

titer

Answer 31

a measurement of how much antibody is produced without actually having to measure the antibody concentration

Question 32

Proactive Vaccination

Answer 32

it may not be necessary to vaccinate all animals to prevent disease transmission within a population; this depends on the disease
ideally this is done with higher risk individuals

Question 33

Reactive Vaccination

Answer 33

it may not be feasible to vaccinate all animals during a disease outbreak. thus a ring vaccination strategy can be employed to contain the disease, and proactive vaccination can be carried out on high risk individuals that are most likely to contribute to the future spread of disease

Question 34

most common causes of failure to respond to vaccination

Answer 34

1. improper storage of live vaccine
2. use of antibodies during administration of a live vaccine
3. poor distribution of an aerosol vaccine
4. poor quality vaccines
5. inappropriate vaccination protocol
6. failure to follow manufacturer’s immunization protocol
7. immunocompromised animal
8. inappropriate antigen in vaccine in the case of the flu vaccine

Question 35

adverse risks of vaccination

Answer 35

1. residual virulence of live attenuated vaccines can lead to disease in immunocompromised individuals
2. local or systemic inflammatory reaction
3. hypersensitivity reactions
4. congenital defects to fetus
5. febrile seizures in children
6. autoimmune disease
7. immune thrombocytopenia purport following MMR vaccination
8. arthritis
   9, encephalitis following measles and mumps vaccine