4-5: Vaccines

Question 1

passive vs. active immunisations

Answer 1

passive is just the transfer of antibodies (maternal, etc.)
- IgG from placenta and IgA from breastmilk

active is usually vaccines
- establish memory with active immunisation

Question 2

passive immunisation

Answer 2

transfer of antibodies

immune protection lasts as long as antibodies are present

does not establish memory
- IgA from breastmilk in digestive track but not blood

examples
- antitoxin (antibodies from horses immunised with toxin)
- human gamma globulin shots (human IgG from donors with many broad antibodies to pathogens)

Question 3

how do vaccines work to provide active immunisation?

Answer 3

active immunisations inducing adaptive immune response similar to immunity/immune memory from a natural infection

provide protection by establishing memory T and B cells
- prevent disease but not infection

Question 4

preventive vs. therapeutic vaccines

Answer 4

preventive
- protection against primary infection and disease
- usually given before exposure

therapeutic
- given to infected/exposed individuals to prevent/reduce disease or stimulate anti-tumour response

Question 5

why the smallpox eradication was the case for vaccine success

Answer 5

no animal reservoir (just in humans)

lifelong immunity from infection/vaccination

one serotype
- little antigenic variation
- no repeat infections

effective attenuated vaccine

Question 6

vaccination routes

Answer 6

mostly intramuscular or subcutaneous
- easiest place to inject but not the greatest immune mechanism

oral vaccines
- live polio and rotavirus

intradermal (between layers of skin)
- way to slowly release antigens

Question 7

adjuvants

Answer 7

help increase inflammation, increase innate immune responses and increase immunogenicity

increased immunogenicity means more help to bind TLRs, more inflammatory responses, and more activation of macs and DCs

some vaccines are just proteins which means there’s no adaptive immune response

Question 8

newer adjuvants (AS01-AS06)

Answer 8

have PAMPs which activate inflammation with TLRs

Question 9

antigenic variation

Answer 9

viruses with many antigenic subtypes and high mutation rates

different viruses circulating at the same time

Question 10

attenuated/live vaccines

Answer 10

live replicating or replication defect (which prevents it from causing more disease in people)

made by growing pathogen in non-human cell culture system until the pathogen is less virulent in human cells
- now made with recombinant DNA technology

low levels or slow replication
- idea that the immune system can get ahead of the virus with slow viral replication

Question 11

advantages of attenuated/live vaccines

Answer 11

very successful (e.g. polio, measles)

self-replicating so low dose and non adjuvant

authentic antigen presentation

more effective to elicit CTLs

Question 12

disadvantages of attenuated/live vaccines

Answer 12

if it replicates, it can infect other people and mutate to a virulent strain (reverse attenuation)

doesn’t deal with strain variability/antigenic variation

Question 13

inactivated vaccines

Answer 13

killed/inactivated organisms/toxins
- inactivated with heat, chemicals, irradiation, etc.

inactivated toxin called a toxoid

Question 14

advantages of inactivated vaccines

Answer 14

no revirulence (higher safety)

Question 15

disadvantages of inactivated vaccines

Answer 15

no replication of pathogens

poor antigen presentation for CTLs
- will need constant boosters

Question 16

live vector vaccines

Answer 16

use of vaccinia as a vector to deliver a piece of RNA or DNA
- recombination with a gene from the pathogen

insert genes from pathogen into a well-characterised vaccine vector

Question 17

advantages of live vector vaccines

Answer 17

self-replicating with no adjuvant

Question 18

disadvantages of live vector vaccines

Answer 18

issue with possible pathogenesis

Question 19

ebola vaccine

Answer 19

live vector vaccine

taking innocuous cow virus, sticking it in a gene from ebola (RNA virus)

virus infects cells but cannot cause disease
- production of antigen from surface protein

live virus with no adjuvant and own PAMPs causing inflammation

Question 20

recombinant protein vaccines

Answer 20

identifying immunogenic proteins and producing large quantities for immunisation

Question 21

advantages of recombinant protein vaccines

Answer 21

potentially less expensive production and very safe

Question 22

disadvantages of recombinant protein vaccines

Answer 22

only protein means no replication of the pathogen
- need adjuvants and boosters
- potentially no long-term memory

Question 23

HPV vaccine

Answer 23

recombinant protein vaccine

vaccinia to express HPV capsid proteins which create virus-like particles (VLPs) to mimic virus structure
- VLPs have no HPV viral DNA

protein creates VLP which has no genome
- VLP fakes looking like a virus so the immune system treats it like a virus

3 immunisations with VLPs and adjuvants
- with no viral DNA, no PAMP so you need this

Question 24

issues with vaccine efficacy

Answer 24

efficacy as how well the vaccine protects the immunised population
- most are >90% protective but influenza is 20-70% protective

potential different efficacy in adults vs. children or immunocompetent vs. immunocompromised individuals

Question 25

issues with vaccine cost

Answer 25

number of people vaccinated vs. cost to manufacture

most original attenuated vaccines cheap
- incredible EOS

Question 26

SARS vaccines

Answer 26

most of them using the spike protein as the main antigen
- few have the whole virus

spike protein is very large which makes it a great antigen

Question 27

different types of vaccines

Answer 27

live attenuated

whole inactivated

split inactivated

synthetic peptides

virus-like particles

DNA/RNA

recombinant subunits

recombinant bacterial vectors

recombinant viral vectors

Question 28

vaccine components

Answer 28

active ingredient
- mRNA containing spike protein gene (like in SARS)

adjuvants
- mRNA doesn’t have adjuvants but is in a lipid
- take out the RNA which encodes for the spike, put it into the RNA vector and surround it with a lipid (liposome)

stabilisers
- sugars added to the component put inside
- outside liposome to keep RNA and lipid stable (makes sure it doesn’t break down)

Question 29

moderna vs. pfizer

Answer 29

both have mRNA inside lipid nanoparticles but different mRNA constructs with different lipid compositions

moderna has full-length spike protein
- pfizer only had part of the spike initially but now has the full-length
- different microgram doses