Formulation

Question 1

give examples of biological sourced materials

Answer 1

1. bioactives- toxins
2. bacterial polysaccharides
3. proteins, peptides, glycoproteins
4. lipids
5. chemically modified substances- subunits

Question 2

give examples of water soluble/dispersible adjuvants

Answer 2

1. cholera toxin
2. synthetic analogues of double stranded RNA (dsRNA)
3. tetanus toxoid

Question 3

give examples of O/W or W/O emulsion adjuvants

Answer 3

1. W/O montanide ISA 720, vegetable oil
2. Freunds complete adjuvant (CFA)- mycobacterium tuberculosis inactivated
   - bacterial cell wall
3. Freunds incomplete adjuvant (IFA)- as CFA but lacks mycobacterium component

Question 4

give examples of what can be used for emulsions in vaccines

Answer 4

1. fats used: silicone oil, light paraffin
2. emulsifiers: fatty acids, polysorbates
3. microcrystalline wax, vitamin E
4. dispersed phase 0.1-0.9 by volume

Question 5

give examples of entrapment or absorption agent adjuvants

Answer 5

1. alum, aluminium hydroxide anhydrous or hydrated
2. silica
3. latex

Question 6

give examples of polymer particles and particulate adjuvants

Answer 6

1. virosomes- virus structured liposomes
2. haemophilus influenzae (Hib)
3. bacterial flagellin

Question 7

give examples of formulation stabilisers

Answer 7

1. freeze drying cryoprotectants- eg sugars such as sucrose
2. buffers- eg amino acids
3. complexing and suspending agents- proteins such as human serum albumin
4. relics- deactivation substrates
5. delivery aids- gums and viscosifiers
6. preservatives
7. co solvents
8. emulsifiers- tween

Question 8

what are antibiotic stabilisers

Answer 8

1. multi use vaccines need special formulation
   - contain antibiotics eg. penicillin used to prevent fungal and bacterial infections
2. used in process septicity and hygiene- eg gentamicin

Question 9

what are chemical inactivation agents

Answer 9

1. chemical remnants- eg. cross linkers are often found in vaccines
   - cross linkers remove pathogenicity and act as a disinfectant
   - formaldehyde remnant, used to inactivate viruses

Question 10

give examples of other inactivations

Answer 10

1. application of heat >60 degrees/10hours
2. low ph acid denaturation
3. irradiation- uv, x ray

Question 11

outline the process of purification of antigens

Answer 11

• eg hep B surface antigen
  1. differential precipitation/solubilisation- ammonium sulphate, ph
  2. ultracentrifugation
  3. gel permeation chromatography
  4. hydrophobic interaction chromatography
  5. tested on enzyme linked immunosorbent assay (ELISA)

Question 12

what is ELISA used for

Answer 12

1. a colour indicating popular micro titre plate type analytic assay of a solution which uses a solid phase immobilised enzyme in an immunoassay to detect the presence of a vaccine antigen
   - used in quality control

Question 13

what are homotypic vaccines

Answer 13

one type of component- eg. Hib, flu

Question 14

what are heterotypic vaccines

Answer 14

many types of antigenic components- eg. TB BCG

Question 15

what is valency

Answer 15

refers to the number of strains used and therefore the universality
- bivalent is 2 strains
- quadrivalent is 4 strains

Question 16

what is gardasil

Answer 16

• polyvalent vaccine for HPV virus
• protects males and females
• comes in prefilled syringe
• compatible with other vaccines
• contains viral proteins and aluminium adjuvant

Question 17

give examples of GSK vaccines

Answer 17

1. boostrix- tetanus
2. fluarix- influenza

Question 18

what is involved in quality control of vaccines

Answer 18

1. sterility- free of live microorganisms
2. chemistry standpoint- correct adjuvant, preservative and ph
3. content- uniformity of content and potency
4. safety- overdosing would carry no effective risk
5. efficacy- each antigen present meets regulatory requirements
6. virulence testing- via passaging in suitable model
7. toxicity- no harm causing constituents
8. stability test- shelf life, optimal storage determination
9. chemical QC- moisture content

Question 19

describe the dosage issues which can be found in vaccines

Answer 19

1. variable- dose, dissipation, response, maturity of immune system
2. constancy of formulation injection properties- viscosity, actives and excipients, stability profile

Question 20

what are the 3 key factors that effective vaccine delivery is based upon

Answer 20

1. efficient encapsulation of the active
2. successful targeting of the active to a specific region of the body and pathogen
3. successful release of that active in situ