Vaccines - bacterial and viral Flashcards
what is variolation
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
what is immunisation
an antigenic stimulus that elecits a specific adaptive immune response
what is a vaccine
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.
what is Ro
number of people that one sick person will infect (on average)
if less than 1 then the infection is halted
average Ro for common diseases
what constitutes the burden of disease
Epidemiology and burden – disability adjusted life years (DALYs)
Economic burden
Mode of Transmission – epidemic vs endemic
definition of herd immunity
immunity when vaccination of sig proportion of pop -> protection for individuals that are not immune
what is the herd immunity threshold
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
briefly summarise effects of adaptive immune response
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.
summarise the immune response to vaccine
- APC present ag (macrophage/DC)
- innate system recognise PAMP and DAMP - present through PRR to APC
- APC present to B and T
- -> cytokines
- activated B undergo division - memory and plasma cells - VDJ recombination
- plasma cells make Ab for vaccine ag
- Ab bind -> neutralisation, Ab dependent cellular toxicity
- macrophages and NK carring Fc bind to Ab -> cell mediated response eg phagocytosis
- if attenuated vaccine - T cell important in destroying infected cell - CD4 bind -> send signal to enable cell mediated response
- memory
immune response post-vaccine
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
what are protective antigens
one that can stimulate an immune response
and prevent/alleviate the clinically important consequences of infection.
some ag not as immunogenic as others
what is an adjuvent
substances of various kinds that enhance immune response
briefly summarise the different types of covid vaccine
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
what are the common components of vaccines
side effects of vaccines
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
what should be considered when planning vaccine service
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
barriers to vaccine
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
childhood vaccine schedule
try to keep gaps to min so can max uptake
what do we need for disease erradication
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
risk of adenoviral vectored vaccine for covid
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
risk of Pfizer vaccine
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
