IC10: Vaccines Flashcards
Describe Inactivated Vaccines
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
Describe Live attenuated vaccines
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)
Describe subunit vaccines
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
Describe conjugate vaccines
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.
Describe recombinant vaccines
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
Describe a type of bacteria in which conjugate vaccines would be useful
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.
Describe toxoid vaccines
Toxic effects of the selected toxin produced by the pathogen are weakened/deactivated with formaldehyde at a certain temperature for a period of time
Describe how toxoid vaccines confer immunity
Toxoids give immunity by stimulating antitoxoid antibodies which bind to the toxin and neutralize its toxic effects
Describe viral vector vaccines
Viral vector vaccines use a modified harmless version of a different virus as a vector to deliver protection.
Describe how mRNA vaccines work
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.
What information should be in the registration file (6)
- 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
What are the parameters of QC tests (5)
- General parameters (pH, appearance)
- Identity (correct identity of antigen)
- Potency (verification of antigen content)
- Purity/integrity of antigen
- Safety (sterility, endotoxins)
What are the components of a vial of vaccine?
1) Immune antigen
2) suspension fluid
3) Preservative
4) Stabilisers
5) Surfactant/emulsifiers
6) Adjuvants
What are some preservatives that can be used in making vaccines?
1) Formaldehyde
2) 2-phenoxyethanol
3) Thimerosal
Name some stabilisers used and their functions.
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)
Name some surfactants/emulsifiers used
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)
Which surfactants/emulsifiers can also be used as adjuvants?
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
Describe the role of adjuvants
Vaccine adjuvants are ingredients used in some vaccines that helps create a stronger immune response in people receiving the vaccine.
Name the 2 groups of adjuvants and state their MOA
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
Name examples of adjuvants
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
What 2 stabilities are more important for vaccines?
Enzymatic stability, thermal stability
State potential problems that may arise from capping procedure
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)
What is typically checked during GMP inspections?
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
What method is used to measure antigen content of recombinant, subunit and inactivated vaccines?
ELISA
