Trends in Vaccinology 1

• LO:


  • Describe the key concepts in vaccinology
  • Understand and evaluate the important milestones of vaccinology

  1. Technological advancements
  2. Types of vaccine
  3. Current schedule (UK)

  • Describe the benefits and limitations associated with different vaccine types/strategies
• Vaccine


  Biological preparation that stimulates the immune system to recognize and defend against a specific pathogen/harmful microbe

  Contains an antigen/mix of antigens from the target pathogen • Live pathogens

  Inactivated pathogens

  Subunits of pathogens

  Genetic material (e.g. mRNA) from the pathogen.

  A method of educating the body’s natural defence against infection/harm

  There are a large variety of vaccine types
• Vaccinology - glossary (Pt. 1)


  • Immunisation - the process of inducing immunity in an individual against a specific pathogen or disease. Vaccines are the primary tools for achieving immunization. Can be ‘active’ or ‘passive’
  • Antigen - a molecule or a part of a pathogen that triggers an immune response. In the context of vaccines, antigens are the key components that the immune system recognizes.
• Vaccinology - glossary (Pt. 2)


  • Immunity - the ability of the immune system to protect the body from infection or disease. Vaccines aim to establish immunity without causing the actual disease.
  • Herd immunity -occurs when a sufficiently high percentage of a population becomes immune to a disease, either through vaccination or previous infection. This reduces the likelihood of disease transmission and protects those who cannot be vaccinated.
• Vaccine: Essentials


  • save 2-3 million globally
  • most effective public health tool after clean water
  • lead to eradication of diseases

  
• Vaccine developments - timeline

  
• Types of vaccine

  
• Current UK schedule

  
• Meningococcal vaccines - indirect effects


  • herd immunity
  • reduction in antibiotic use
  • cost effective
  • Shift in serotype prevalence
  • global health impact
• Vaccine delivery: systemic vs mucosal


  • The route of vaccine delivery can impact on the magnitude, quality, and locations, of immune response
  • Most vaccines are given via the intramuscular (i.m) or subcutaneous (s.c) route

  
• Nasal flu vaccine (LAIV)


  • LAIV – Live attenuated influenza vaccine • Delivered mucosally (nasal spray)
  • Live trivalent A(H1N1) A(H3N2) B

  1. From 2014 quadrivalent with 2 Bs

  • Seasonal vaccine – reformulated annually
  • Licensed ages 2-18y
  • Programme rolling out in UK

  1. 2013 all 2 & 3 year olds, pilots in schools
  2. 2014 all 2 3 & 4 year olds + schools pilots
  3. 2015-16 5-6-7 year olds added

  • Delivered mucosally (nasal spray)
  • Seasonal vaccine – reformulated annually
• Nasal flu vaccine (LAIV)



  • LAIV – Live attenuated influenza vaccine • Delivered mucosally (nasal spray)
  • Live trivalent A(H1N1) A(H3N2) B

  1. From 2014 quadrivalent with 2 Bs

  • Seasonal vaccine – reformulated annually
  • Licensed ages 2-18y
  • Programme rolling out in UK

  1. 2013 all 2 & 3 year olds, pilots in schools
  2. 2014 all 2 3 & 4 year olds + schools pilots
  3. 2015-16 5-6-7 year olds added

  • Delivered mucosally (nasal spray)
  • Seasonal vaccine – reformulated annually

  
• Excess respiratory mortality

  
• Vaccine delivery: systemic (parental)


  Parenteral

  • Most established route of vaccine
  • Many different delivery options
  • Elicits systemic immune response
• Vaccine delivery: mucosal


  Pros:

  • early control of infection
  • effective control of non-invasive infections
  • Obviates need for injection
  • wide-spread responses

  Cons:

  • difficult to induce effective IgA response in practice
  • antigen instability at mucosal sites
• Human Papilloma Virus (HPV)


  • Over 100 types
  • Some can cause cervical and penile cancer (oncovirus)
  • Some cause warts
  • Harald zur Hausen –identified some HPVs as oncogenic
• HPV Vaccines –Virus Like Particles


  • 3 vaccines

  1. Bivalent 16 & 18 cancer causing types
  2. Quadrivalent 6 & 11 genital wart causing types plus !6 & 18
  3. Nonavalent – quad plus 5 more types

  • 2 (originally 3) doses over 6 months
  • Mostly used in teenage girls to date

  
• Genital Warts in Australia

  
• Australia – Cervical High Grade abnormalities

  
• WHO policy – elimination of cervical cancer


  • Massive roll out: shortages
  • Biggest impact is in females before sexual debut
  • Until more vaccine is available – giving to older girls/women and to boys will prevent less cancer than giving vaccine to 11 year old girls

  
• Malaria vaccines – recent progress



  • Malaria is caused by parasites from the Plasmodiumgenus
  • Causes ~400,000 deaths per year (mostly children)
  • Complex life cycle
  • Attenuated or killed parasites not deemed suitable for a vaccine
  • Immune evasion
  • Antigenic shift in blood stage

  
• Malaria vaccine development


  • RTS ,S/ASO1 -2015

  1. 36% efficacy against clinical malaria (32% efficacy against severe malaria) & wanes rapidly
  2. VLP formulationUses
  3. P. falciparum circumsporozoite protein (CSP) antigen
  4. Fused with hepBsurface antigen as a scaffold to display CSP
  5. Targets pre-erythrocytic stage

  • R21 /Matrix-MTM - 2023

  77% efficacy durable for at least 2y

  Improved formulation: increase antigen dose, new adjuvant (Matrix M)

  Cheaper

  Thermostable

  Will need to vaccinate 40million children/per

  
• Types of vaccine (Pt. 1)

  
• Types of vaccine (Pt. 2)

  
• Summary:


  • Vaccination; best tool for prevention of infectious diseases
  • Vaccine strategies can adapt depending on the challenge
  • No single vaccine technology is perfect for all pathogens & scenarios

  1. mRNA –fast protection in viral outbreaks
  2. Protein conjugate– durable protection against bacterial infections
  3. VLP –strong antibody responses
  4. Viral vectored vaccines – strong T cell responses

  • Each vaccine is very different

  1. Basic research into the microbiology and immunology of different infections is crucial
  2. Different strategies are used in different situations (populations/setting)