37 Immunisation Against Infectious Disease

Question 1

What is immunisation?

Answer 1

Using vaccines or antibody‐containing preparations to provide immune protection vs. specific diseases.

Question 2

What are the two main types of immunisation?

Answer 2

• Active (vaccination)
• Passive (e.g. provision of antibodies)

Question 3

What are the advantages and disadvantages of passive immunisation?

Answer 3

Advantages:

• Immediately active
• Effective for post‐exposure prophylaxis
• No need for fully functional immune system (e.g. use in immunocompromised hosts, young, elderley)

Disadvantages:

• No memory
• Short-lasting

Question 4

Describe passive immunisation and what it involves.

Answer 4

Passive immunisation involves intravenous immunoglobulins (IVIg), which is a mixture of antibodies that is administered intravenously. These can be in different forms:

• Mix of standard immunoglobulins from animal/human donors
  
  • Contains multiple different antibodies
  • Non-specific -> Effective against many vaccines
• Human hyperimmune serum (high titre)
  
  • Similar to the normal mix, but it is produced from plasma from donors with a high titre of antibodies to a specific pathogen
  • Specific -> Effective against a single pathogen

Question 5

Give two examples of diseases treated using passive immunisation.

Answer 5

• Rabies
• Hepatitis B

These are conditions where rapid response is required, so the IV antibodies are useful.

Question 6

What are the different types of active immunisation?

Answer 6

*Live attenuated vaccines
*Live and subunit vaccines
*Vectored vaccines
*mRNA vaccines

Question 7

What is a live attentuated vaccine and how does it work?

Answer 7

• Administration of either an attenuated form of the pathogen or an immunologically related organism
• The organism multiplies inside the human host and provides strong antigenic stimulation
• It provides prolonged immunity (years to life), often with single dose
• Vaccine often provides cell‐meditated immunity

Question 8

What are the advantages and disadvantages of live attenuated vaccines? [EXTRA]

Answer 8

Advantages:

• Lost-lasting immunity
• Easy to administer
• Inexpensive production
• Induces the cell-mediated response (as well as the humoral response)

Disadvantages:

• Can revert to virulent form
• More severe reactions than killed vaccines
• Cannot be given to immunocompromised patients
• Difficult to store due to heat lability

Question 9

Give examples of disease that have live attenuated vaccines.

Answer 9

*Measles
*Sabin polio vaccine
*BCG

Question 10

Give an example of an immunologically related organism that has been used in a live attenuated vaccine.

Answer 10

Vaccinia (basically cowpox) used as a vaccine for smallpox.

Question 11

How are killed/inactivated vaccines developed?

Answer 11

Chemical treatment of antigen preparation (via heat/ formaldehyde) to inactivate infectivity and toxicity of whole organisms.

Question 12

Give examples of diseases with killed vaccines.

Answer 12

Cholera, pertussis (whooping cough), seasonal flu.

Question 13

What are subunit vaccines and how do they work?

Answer 13

*They are derived form genetically engineered protein subunit
* Vaccines that contain a fragment of the pathogen and elicits an appropriate immune response
* The fragment may be:
* Protein -> Toxoid (inactivated toxin) or cell-surface antigen
* Polysaccharide -> Found in capsule of some bacteria
* Conjugate (of two antigens)

Question 14

Give some examples of diseases that can be vaccinated against using subunit vaccines.

Answer 14

*HBV, HPV
* Toxoid
* Tetanus toxoid
* Diphtheria toxoid
* Genetically engineered subunit
* Influenza

Question 15

What are toxoids?

Answer 15

• Derivatives of bacterial exotoxins that are inactivated.
• Rendered non‐toxic by treatment with chemicals or by genetic engineering but remain immunogenic
• They are used in subunit vaccines

Question 16

What are conjugate vaccines and how do they work?

Answer 16

• They are a type of subunit vaccine
• A weak desired antigen (polysaccharide) is combined with a stronger antigen (usually a protein), which acts as a carrier to increase the immunogenicity of the weak antigen creating a stronger and longer-lasting immune response.
• The protein carrier provides peptides for MHC presentation, thus providing T cell help for polysaccharide-specific B cells to make antibodies
• It is often used to increase the response to polysaccharides in the bacterial cell wall

Question 17

What principle do conjugate vaccines demonstrate and how do they demonstrate this principle?

Answer 17

linked recognition
*Coupling of weak antigen to carrier helps induce a T-cell activation via MHC which then can activate B-cells.

Question 18

Why do B cells activated by T cells provide greater immunity?

Answer 18

T cell dependent activation leads to the generation of memory B cells

Question 19

What is vaccine escape and how can it be overcome?

Answer 19

• Vaccine escape is the loss of effectiveness of a vaccine in combating a certain pathogen
• It is usually due to recombination of DNA encoding antigens, so that the antigens are no longer recognisable by the immunoglobulins that the body produces
• This could perhaps be overcome by combining multi-component polysaccharide conjugate vaccines

Question 20

What are the issues surrounding the MMR vaccine?

Answer 20

Unwarranted fears about the combined live attenuated MMR vaccine and autism saw the uptake of the MMR vaccine fall from 92% to 84%
Lead to small outbreaks of measles and mumps in London due to the reduced herd immunity

Question 21

What are vectored vaccines and how do they work?

Answer 21

• Use of non-pathogenic viral vectors to carry genetic material (recombinant DNA) encoding vaccine antigens in order to elicit an immune response against them.

Question 22

What is the vector and antigen used in the vectored vaccine against HIV?

Answer 22

• Vector -> Adenovirus, Pox virus
• Antigen -> HIV gag

Question 23

What is the antigen used in the vectored vaccine against SARS-CoV-2?

Answer 23

Spike protein

Question 24

What sort of response do vectored vaccines aim to elicit?

Answer 24

Designed to primarily elicit T cell responses.

Question 25

What are adjuvants?

Answer 25

• Agents that are added to a vaccine in order to improve the immune response to the vaccine.
• Examples include aluminium hydroxide and paraffin oil.

Question 26

How do adjuvants work?

Answer 26

• Act as a depot for the antigen, presenting the antigen over a longer period of time, thus maximizing the immune response before the body clears the antigen.
• Can include PAMPs to stimulate innate immunity via PRRs.

Question 27

How do PAMPs function as adjuvants?

Answer 27

Stimulate the innate immune system (PRRs) such as TLR4 to LPS which induces shock to mimic the action of Gram negative bacteria
LPS derivatives can therefore be used which has a lower toxicity

Question 28

How do mRNA vaccines work?

Answer 28

mRNA delivered in lipid nanoparticles

Question 29

Why and how are is the mRNA in mRNA vaccines modified?

Answer 29

Nucleoside modification to enhance stability of the mRNA encoding the antigenic protein: mRNA has pseudouridine instead of uracil which enhances mRNA stability and transcriptability
Pseudouridine is an isomer of uridine in which uracil is attached via C-C instead of N-C glycosidic bond

Question 30

Give examples of mRNA vaccines.

Answer 30

BioNTech or Moderna vaccines encoding spike protein of SARS-CoV 2.

Question 31

Why are viruses more difficult to vaccinate against than bacteria?

Answer 31

Viruses are obligate intracellular pathogens and cannot be reached by antibodies during their replication so a T cell response is required to eradicate them