Vaccines - bacterial and viral

Question 1

what is variolation

Answer 1

Deliberate infection with smallpox with the hope that a mild infection and subsequent protection would result

Dried smallpox scabs were blown into the nose or inoculated through a puncture in the skin.

less died when variolated compared to number that died with natural infection

Question 2

what is immunisation

Answer 2

an antigenic stimulus that elecits a specific adaptive immune response

Question 3

what is a vaccine

Answer 3

a biological product
that can be used to safely induce an immune response
that confersprotectionagainst infection and/or disease
on subsequent exposure to a pathogen.

Question 4

what is Ro

Answer 4

number of people that one sick person will infect (on average)

if less than 1 then the infection is halted

Question 5

average Ro for common diseases

Answer 5

Question 6

what constitutes the burden of disease

Answer 6

Epidemiology and burden – disability adjusted life years (DALYs)

Economic burden

Mode of Transmission – epidemic vs endemic

Question 7

definition of herd immunity

Answer 7

immunity when vaccination of sig proportion of pop -> protection for individuals that are not immune

Question 8

what is the herd immunity threshold

Answer 8

HIT = 1-1/Ro

percentage of fully immune individuals needed to stop the spread of disease

vaccine effectiveness needs to be taken into account when considering vaccine coverage

Question 9

briefly summarise effects of adaptive immune response

Answer 9

Antibodies:
* Neutralisation of infectivity owing to binding of viral surface antigens
* Destruction of infected cells – antibody dependent cellular cytotoxicity.
* Macrophages and NK cells carrying Fc receptors bind to the antibodies.

Activated CD8 T cells liberate interferon gamma and TNF alpha destroying virus infected cells.

Question 10

summarise the immune response to vaccine

Answer 10

1. APC present ag (macrophage/DC)
2. innate system recognise PAMP and DAMP - present through PRR to APC
3. APC present to B and T
4. -> cytokines
5. activated B undergo division - memory and plasma cells - VDJ recombination
6. plasma cells make Ab for vaccine ag
7. Ab bind -> neutralisation, Ab dependent cellular toxicity
8. macrophages and NK carring Fc bind to Ab -> cell mediated response eg phagocytosis
9. if attenuated vaccine - T cell important in destroying infected cell - CD4 bind -> send signal to enable cell mediated response
10. memory

Question 11

immune response post-vaccine

Answer 11

Entry of pathogen activated memory T cells
-> immune response

Memory B cells become active plasma cells (more antibodies produced at a faster rate)

Memory killer T cell response may be reactivated

Question 12

what are protective antigens

Answer 12

one that can stimulate an immune response

and prevent/alleviate the clinically important consequences of infection.

some ag not as immunogenic as others

Question 13

what is an adjuvent

Answer 13

substances of various kinds that enhance immune response

Question 14

briefly summarise the different types of covid vaccine

Answer 14

inactivated
* chemically/physically inactivated virus in culture
* cannot cause disease

live attenuated
* weakened version
* limited replication extent
* active but not as immunogenic
might culture in a non-human like tissue
* closely resemble natural pathogen

viral vector vaccine
* adapts safe modified viral vectors to express covid protein / genetic material
* astrazeneca

DNA vaccine
* contain circular DNA
* encode protein of interest

RNA vaccine
* Pfizer/moderna
* use own ribosomes to make mRNA -> immune response
* mRNA packed in lipid nanoparticles

recombinant subunit vaccine
* synthetic nanoparticles
* coated in purified viral ag

virus like particles vaccine
* contains multiprotein structures that mimic virus yet devoid of viral genome

Question 15

what are the common components of vaccines

Answer 15

Question 16

side effects of vaccines

Answer 16

injection site pain,
redness
swelling
some systemic symptoms
* fever,
* malaise
* headache

all occur in 1-2 days - reflect inflammatory and immune responses that -> immunity

from MMR - fever, rash, febrile seizure

Question 17

what should be considered when planning vaccine service

Answer 17

should be administered before the age related peak incidence of the disease
* vaccinate before passive immunity wanes
* but want immune system mature enough that they can respond

Targeted vs widespread

To eliminate a disease the effective R0 needs to be less than 1

?requirement for catch up campaigns.

Surveillance of Disease incidence and Adverse events before and after implementation of vaccination

Question 18

barriers to vaccine

Answer 18

Wakefield
absence of health infrastructure
lack of convenient provision
lack of financial resources
marginalisation
anti-vaccination

lack of trust - examples where used to sterilise people etc - esp lower socioeconomic backgrounds

Question 19

childhood vaccine schedule

Answer 19

try to keep gaps to min so can max uptake

Question 20

what do we need for disease erradication

Answer 20

No animal reservoir

Antigenically stable pathogen with only one (or small number of) strains

No latent reservoir of infection and no integration of pathogen genetic material into host genome

Vaccine must induce a lasting and effective immune response

High coverage required for very contagious pathogens

Question 21

risk of adenoviral vectored vaccine for covid

Answer 21

Vaccine-induced Thrombotic Thrombocytopenia 4-42 days post infection
Clot anywhere (mostly CVST)
PF4 antibodies
Tx IVIg +/- PLEX
Young adults, who are at less riks of covid, viral vector -> immune response inc thrombosis in sinus

capillary leak syndrome

Question 22

risk of Pfizer vaccine

Answer 22

Myocarditis 5.8/millionyoung adults + adolescent males. 2-3 days after 2nd dose
Young adult men
What is the threshold for vaccination so benefits outweigh risk