Lecture 12: Memory and vaccines

More antigen-specific lymphocytes

Long-lived plasma cells in bone marrow

Memory B cells

Memory T cells in lymphoid organs and tissues

Eurasia

Always circulating

30% mortality rate

North American Colonization

90% mortality rate

1900s

~ 300 million deaths

Variolation

Dried smallpox scap powder inhaled or transferred into cuts

Vaccination

Inoculated with cowpox via small poke

Modern vaccination

Infection with live vaccinia virus

Closely related to horsepox

Applied with bifurcated needel

mRNA vaccine

Approach: Inject with mRNA that encodes target antigen

Pros: Can vaccinate against any protein, Easy to modify and update

Cons: Unstable, ultra cold storage

Subunit vaccine

Approach: Administer pathogen protein component paired to adjuvant

Pros: Very stable, no containment requirements

Cons: Need an adjuvant, stable but cannot be frozen, multiple doses required

Live attenuated vaccine

Approach: Infection with related but less harmful pathogen

Pros: 1 dose= strong immune activation, multiple of all epitopes present, activation in relevant tissues

Cons: Storage and transport, can cause disease in susceptible people, can revert to disease-causing form

Inactivated vaccine

Approach: Kill pathogen, then administer

Pros: Stable, easy to store, cannot cause disease

Cons: 3D pathogen structure maintenance is difficult, weaker immune response- booster required

Recombinant (viral) vector vaccine

Approach: Take surface protein from a harmful pathogen, Engineer a harmless virus to express that surface protein

Pros: 1 dose= strong immune activation, fast redesign, some are quaternary stable

Cons: Immune response also against vector (VSV), unstable, ultra cold storage

Toxoid vaccine

Approach: Administer pathogen toxin paired to adjuvant

Pros: Cheapest of all options, well understood (new vaccines require minimal testing)

Cons: Needs an adjuvant, stable but cannot be frozen, injection only, multiple doses required, personal protection (not community)

Conjugate vaccine

Approach: Bacterial sugar attached to carrier protein, immune system treats the sugar like protein, generating a stronger response

Pros: High quality anti-sugar antibodies, Effective in infants, stable storage and shipment

Cons: Many sugars used by different bacteria, use can change, multiple doses needed, difficult to grow and prepare

Vaccine components

1. Active ingredient/antigens

2. Adjuvants

3. Stabilizers

4. Preservatives

5. Water, salt, buffers

6. Deliver ingredients

7. Manufacturing traces

Herd immunity

R0= average # of people 1 case infects in a susceptible population

Threshold= 1-1/R0

Not everyone can be vaccinated

Immunodeficient

Age (very young/old)

Allergies to vaccine components