Drug discovery (4)- vaccine

Question 1

Vaccines

Answer 1

• Vaccines =>
• Prevent disease =>
• Saving 10s of millions of lives

Question 2

Misinformation

Answer 2

• Complacency
• Ignorance arrogance
• Religion
• Solipism
• Scientific and clinical consensus: vaccines are the best medicine humanity has ever created

Question 3

Vaccine induce protective immunity

Answer 3

• Productive immunity is an enhanced adaptive immune response to re-infect
• Prophylactic
  
  • Prevent or ameliorate the effects of a future infection by a natural pathogen
• Therapeutic
  
  • Treat or ameliorate existing condition
  • Cancer vaccines/Addiction vaccine
• Vaccinology is the science of vaccine discovery and development

Question 4

Herd Immunity

Answer 4

Question 5

Vaccine History

Answer 5

• Centuries of empirical development have led to a limited number of vaccines controlling major IDs (anti-biotics) =>
• Last 40 years have registered a few but innovative ID Px vaccines with blockbuster potential (Anti-biotic resistance; emerging disease; Resurgent disease) ==>
• R&D pipeline is full of new ID Px and now Rx vaccines for multiple chronic diseases

Question 6

Variolation

Answer 6

• Ancient practice used throughout the world
• Involved transferring pus from a survivor’s scab to an unaffected person
• No consensus on why this worked: route of administration, attenuation, passive immunization, virus killed by transfer combination of all of these and more
• Violent opposition from sections of the public- Prefigures modern anti-vaccine movements
• Yet seen by some historians as the first systematic public initiative

Question 7

N^o of vaccines and sales

Answer 7

Question 8

Types of vaccine

Answer 8

• Live attenuated- live virus but virulence (severity) is reduced
  
  • BCG vs TB; Mumps; Sabin Polio; Varicella; Rubella
• Inactivated or Killed pathogen
  
  • Flu; cholera; Salk polio; plague; Rables
• Sub-unit or Toxoid- individual proteins
  
  • Diptheria; Tetanus; Hepatitis B; Lyme disease
• Carbohydrate (epitope)
  
  • New typhoid; meningococcal; Haemophilus B

Question 9

What makes a vaccine

Answer 9

• Biological component
  
  • Whole organism, protein, epitope
• Adjuvant -molecule which can increase the initial immune response (important for epitope and sub-unit vaccine)
  
  • Alum, AS009, AS008, experimental adjuvants
• Delivery mechanism
  
  • Raw recombinant protein; liveviral vector DNA loaded onto APC’s liposomes

Question 10

Delivery technology

Answer 10

• Raw vaccine prep
• Recombinant protein
• Live viral vector; Live bacterial vactor; Naked DNA
• Loaded onto APC’s
• Liposomes

Question 11

Adjuvants

Answer 11

• ALUM
  
  • Aluminium Phosphate: AlPO₄
  • Aluminium Phosphate: Al(OH)₃
• Oil-in-Water
  
  • Squalene-based adjuvants
  • MF59
  • AS03

Question 12

Biological component

Answer 12

• Whole organism (attenuated)
• Sub-unit vaccine
• Epitope vaccine

Question 13

Adaptive immune response to pathogen or vaccination

Answer 13

• Antigen Presenting Cell- Vaccine binds to this cell
• Helper T Cell is activated
  
  • Release of IL-2 which acts on autoreceptors as well as CTL cells
  • IL-4 and IL5 is release to activate B cells
• B cells can also be activated by viral protein
  
  • Differentiation Ab production
  • Activation memory cells

Question 14

Immune system has 2 arms

Answer 14

• Humoural (Ab mediated)
• Cellular (MHC-TCR mediated)
• Most vaccines mediate by Abs
• Low hanging fruit all harvested
• Need to target Cellular Immunity to address diseases without effective vaccines

Question 15

Cellular Immune response

Answer 15

Question 16

Conventional Subunit vaccine discovery

Answer 16

Question 17

Reverse Vaccinology

Answer 17