Lecture 2- memory and vaccination

Question 1

what are the objectives?

Answer 1

• The cellular basis of immunological memory and how this allows
  vaccine induced immunity
• Current status of vaccination in the UK (see 2X Fundamental topics
  in Biology)
• New/experimental approaches to vaccine design - Live Recombinant
  vaccines
• What vaccine adjuvants are and their functions in vaccine
  formulations
• New/experimental approaches to vaccine design - Nucleic Acid
  vaccines
• The current status of research into SARS-CoV-2 vaccines

Question 2

what are the protein / adjuvant vaccines?

Answer 2

• Sanofi/GSK vs Novavax vaccine trials
• Novavax - Spike protein formulated in Matrix M adjuvant
• Sanofi/GSK - Spike protein formulated in AS04 - Alum and
  MPLA (TLR4 agonist)

Question 3

what are the clinical uses of adjuvants?

Answer 3

• adjuvant activity of Aluminium precipitates first described in
  1926
• was the only adjuvant approved for human vaccines in UK until
  2007
• a component of:
  – Diphtheria, Tetanus, Pertussis, Inactivated Polio, Meningitis C,
  B, ACWY, Pneumococcus, Hemophilus Influenzae, Hepatitis A,
  Hepatitis B vaccines, Gardasil.
• Induces Th2 responses

Question 4

why study adjuvants?

Answer 4

• Non-living vaccines do not
  stimulate strong immune
  responses —> Adjuvants can
  provide this stimulus
• Adjuvants have a broad range of
  positive effects on vaccine
  performance
• Adjuvants are a critical factor in
  vaccine development

Question 5

what are adjuvants?

Answer 5

“Agents which act non-specifically to
increase the specific immune response
or responses to an antigen”
The Dictionary of Immunology
“the immunolgists dirty little secret”
Charles Janeway

Question 6

what are features of memory T cells?

Answer 6

• Increased frequency.
• Lower activation thresholds
• Better effector function
• Changes in expression of adhesion molecules, eg. CD44,
  ICAM-1, LFA-1,LFA-3 & α4-integrin, as well as chemokine
  receptors.
• Altered migration pathways (Tcm/Tem)
  T Memory cells have faster/ better effector function
  Different migratory capacities of T memory cells

Question 7

what are conjugate vaccines?

Answer 7

• High titres/high affinity/class switched Ab
  against carbohydrates protect against e.g.
  Haemophilus Influenzae and
  Meningicoccal infections
• BUT! Carbohydrates can’t induce high
  titre/affinity/class switched Ab responses.
• Because T cells can’t respond to
  carbohydrates (they only recognise
  peptides in the context of MHC) —>
  You don’t get T cell help for B cell Ab
  production (no germinal centre
  reaction)

Question 8

what are the features of memory b cells?

Answer 8

• Increased frequency
• Express switched isotypes (IgG, IgA, IgE).
  –Better effector function (e.g. complement activation,
  opsonisation)
• Express somatically mutated Ig V genes.
• Express higher affinity Ig.
• Lower activation thresholds/Faster formation of Plasma Cells

Question 9

why are secondary Ab responses better?

Answer 9

• The Germinal Centre reaction drives affinity maturation and
  class switching of Memory B cells and Long Lived Plasma Class

Question 10

how to conjugate a carbohydrate to a protein?

Answer 10

1. B cell receptors recognise Hapten
2. Conjugate is internalised and carrier
   degraded into peptides
3. Peptides are presented to T cells in context of MHC II.
4. Peptide (carrier) specific T cells recognise peptide/MHCII
5. Carrier specific T cells provide
   B cell help

Question 11

what are attenuated recombinant vaccines?

Answer 11

• Insert protective antigen genes into attenuated pathogen to act as
  a carrier
• Mostly Viruses (eg. Vaccinia, Adenovirus)
• Live Attenuated Influenza Vaccine (LAIV) - (see 2X Fundamental
  topics in Biology)
• Replication defective e.g.
  – Modified Vaccinia Ankara (Malaria, TB & HIV)
  – Adenovirus - ChAdOx, Ad5, Ad26 (SARS-CoV-2)

Question 12

what are the 10 threats to global health in 2019?

Answer 12

• Air pollution and climate
• NCD
• Flu pandemic
• Fragile and vunerable settings
  (e.g. weakened health
  services)
• AMR
• Ebola and other high threat
  pathogens
• Weak primary care
• Dengue
• HIV
• Vaccine hesitancy

Question 13

what vaccines require thI immunity?

Answer 13

• Bacterial
  – Tuberculosis
  – Leprosy
• Viral
  – HIV
  – Influenza
• Parasite
  – Malaria
  – Leishmaniasis

Question 14

what do nucleic acids vaccines have?

Answer 14

a built in adjuvant
* TLR3, TLR7, TLR8 and TLR9
* All recognise Nucleic Acids
* To sense viral infections