IC10: Vaccines

Question 1

Describe Inactivated Vaccines

Answer 1

They contain bacteria or viruses that have been heat or chemically inactivated. These vaccines produce a weak immune response and require repeated doses to build up and/or maintain immunity. They are considered safer than live attenuated vaccines

Question 2

Describe Live attenuated vaccines

Answer 2

These vaccines contain a version of the living virus or bacteria that has been weakened so that it does not cause serious disease in people with healthy immune systems (still alive but no pathogenicity)

Question 3

Describe subunit vaccines

Answer 3

They are vaccines that include only specific parts of the virus or bacteria, or subunits, instead of the entire germ. Parts can include spike proteins, peptides or polysaccharide

Question 4

Describe conjugate vaccines

Answer 4

A type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.

Question 5

Describe recombinant vaccines

Answer 5

Genes that encode for specific antigens of the virus or bacterium against which we want to protect against is taken and inserted into the manufacturing cells. Once cell uptakes the genes, they are able to secrete desired antigens which are collected and made into vaccine

Question 6

Describe a type of bacteria in which conjugate vaccines would be useful

Answer 6

Bacteria that has antigens with an outer coating of polysaccharides. Antigens are able to be disguised by the polysaccharides and escape detection by an immature immune system i.e child immune system.

Question 7

Describe toxoid vaccines

Answer 7

Toxic effects of the selected toxin produced by the pathogen are weakened/deactivated with formaldehyde at a certain temperature for a period of time

Question 8

Describe how toxoid vaccines confer immunity

Answer 8

Toxoids give immunity by stimulating antitoxoid antibodies which bind to the toxin and neutralize its toxic effects

Question 9

Describe viral vector vaccines

Answer 9

Viral vector vaccines use a modified harmless version of a different virus as a vector to deliver protection.

Question 10

Describe how mRNA vaccines work

Answer 10

mRNA vaccines work by introducing a piece of mRNA that corresponds to a viral protein (usually found on the virus outer membrane) into host cell. Antigen (spike protein) produced in cells to induce immune response.

Question 11

What information should be in the registration file (6)

Answer 11

• Any biological materials used in the process need to be screened for possible contaminants (bacteria, viruses)
• Process, process controls, QC tests need to be described
• Containers and process equipment has to be evaluated for possible leaching of elements into the vaccine
• Impurity removal capacity of process needs to demonstrated
• Assessment has to be made confirming the safety of the product
• Any residuals need to be below acceptable safety limits

Question 12

What are the parameters of QC tests (5)

Answer 12

• General parameters (pH, appearance)
• Identity (correct identity of antigen)
• Potency (verification of antigen content)
• Purity/integrity of antigen
• Safety (sterility, endotoxins)

Question 13

What are the components of a vial of vaccine?

Answer 13

1) Immune antigen
2) suspension fluid
3) Preservative
4) Stabilisers
5) Surfactant/emulsifiers
6) Adjuvants

Question 14

What are some preservatives that can be used in making vaccines?

Answer 14

1) Formaldehyde
2) 2-phenoxyethanol
3) Thimerosal

Question 15

Name some stabilisers used and their functions.

Answer 15

1) Monosodium glutamate (MSG): protects vaccines from heat, light, humidity or acidity while they are stored

2) Gelatin: protect vaccines from heat while they are stored

3) Sorbitol: stabilizes proteins when in solution

4) Buffers: (monopotassium phosphate, sodium borate and sodium chloride) adjust tonicity and maintain osmolarity (by preventing osmosis from killing cells)

Question 16

Name some surfactants/emulsifiers used

Answer 16

1) Sorbitan esters

2) Lecithins

3) Mannide oleates

4) Lipopolysaccharides (LPS) from the external membranes of Gram-negative bacteria

5) Saponins

6) Dimethyl dioctadecyl ammonium bromide (positively charged organic salt) (DDAB)

Question 17

Which surfactants/emulsifiers can also be used as adjuvants?

Answer 17

1) Lipopolysaccharides (LPS) from the external membranes of Gram-negative bacteria

2) Saponins

3) Dimethyl dioctadecyl ammonium bromide (positively charged organic salt) (DDAB)

4) Montanide

Question 18

Describe the role of adjuvants

Answer 18

Vaccine adjuvants are ingredients used in some vaccines that helps create a stronger immune response in people receiving the vaccine.

Question 19

Name the 2 groups of adjuvants and state their MOA

Answer 19

1) Vaccine delivery systems.
Use of microparticles and nanoparticles to concentrate and target the antigen

2) Immunostimulatory adjuvants.
Activate innate immunity directly (cytokines) or through pattern recognition receptors (PRRs) when used in combination with the active ingredient

Question 20

Name examples of adjuvants

Answer 20

1) Aluminium salts principally aluminium phosphate and hydroxides

2) Complete Freund’s adjuvant

3) Oil in water (o/w) or water in oil (w/o) emulsions (e.g MF59 is a submicron o/w emulsion which contains squalene (influenza vaccine))

4) Montanide

Question 21

What 2 stabilities are more important for vaccines?

Answer 21

Enzymatic stability, thermal stability

Question 22

State potential problems that may arise from capping procedure

Answer 22

1) Trap moisture: although moisture trapped is supposed to be sterile, it may not be = (a form of microbial contamination)

2) Need lubrication to ensure that rubber stopper does not breakdown during closing step which may introduce foreign particles and contaminate product.
* But lubricant may also be a possible source of contamination

3) Possible source of contamination (rubber debris; see above point)

Question 23

What is typically checked during GMP inspections?

Answer 23

1) Compliance with GMP guidelines

2) Full traceability (batch number on vaccine can be traced to batch number of ingredients used, name of operator who produced it, machine used to produce and test it, if machine has been properly maintained etc.) Ensures that if there is a problem, the problem can be traced.

3) Manufacturing and testing done as described in registration file

4) Quality of raw materials: properly tested as described in registration file

5) Analytical QC methods are properly validated

6) Results within acceptance limits for process controls

Question 24

What method is used to measure antigen content of recombinant, subunit and inactivated vaccines?

Answer 24

ELISA

Question 25

What method is used to measure potency of live attenuated vaccine?

Answer 25

In-vitro cell cultures to measure virus titre

Question 26

What parameters are used to measure potency of polysaccharide vaccines

Answer 26

Polysaccharide content

Polysaccharide size

Purity

Degree of adsorption (for vaccines that are adsorbed on aluminium)