Challenges of vaccine design L29 Flashcards
(28 cards)
virus like particles VLP
these are molecules that mimic the structure of the virus but lacks viral genetic material so are not infectious
made of viral structural proteins that self-assemble into particles
no DNA or RNA so cannot replicate or cause disease
looks like a virus so immune system is triggered
non enveloped VLPS
just viral caspid proteins that assemble into a shell, often made in yeast cells
stable the enveloped types
good for vaccines and easier and cheaper to produce
enveloped VLPS
eVLPs
have caspid core proteins with lipid envelope with embedded viral glycoproteins
made usually in mammalian cells in order to form lipid envelope
less stable as sensitive to temp and pH
outer membrane vesicles vaccines
OMVs are small, naturally immunogenic- triggering immune system without full bacteria
contain bacterial antigens, LPS, and proteins
stimulates innate and adaptive immunity
can be engineered to present specific antigens
no genetic material so cannot replicate
natural adjuvants to enhance immune response
multivalent so can present multiple antigen s at once
stable and easy to store
protein polysaccharide conjugate vaccines
these are a type of vaccine where the sugar molecular from a bacterial surface is linked (conjugated) to a protein to enhance the immune response
protein = carrier protein
this linkage makes the polysaccharide more immunogenic
induces memory B T cells
works for infants
affinity maturation
intranasal delivery route
good for mucosal and lung immunity but safety issues in humans
oral delivery route
cheap mass vaccination and mucosal immunity but bad stability of vaccine in GI tract
intramuscular delivery route
good as clinically relevant and has systemic immunity but needle is required
intraperitoneal delivery route
good to be used for some candidate cancer vaccines however there are safety issues
aerosolised delivery route
good as muscle and lung immunity, and mass vaccination with nebuliser or inhaler or spraying onto animals
bad as safety issues in human
intradermal delivery route
good as clinically relevant and system immunity but needle is requiredi
what are vaccine adjuvants
these enhance and direct adaptive immune response to vaccine antigens that otherwise might lead to tolerance
adjuvant action
some can active DC by mimicking components of microbes that bind to PRRs on APC
role of DC in vaccination
similar to response to pathogen
immature DC digests antigens from pathogen and displays on surface (antigen uptake and activation)
migrates to LN
matura DC interacts with T B cells to launch specific adaptive response to pathogen
critical mechanistic criteria of an adjuvant
- extent the presence of antigen
- locally activate macrophages and lymphocytes
- support local production of cytokines
- activate antigen presenting cells, support absorption, migration and present antigen
benefits of vaccine adjuvants
enhance or accelerate the immune response
prolong the immune response
focus the immune response
diversify the immune response
increase antibody affinity
improve long term memory
special patient populations
dose sparing
risks of vaccine adjuvants
increase reactogenicity - local or system effect
nonspecific immune activation - immune mediated disease, organ specific, inflammatory disease
advantages of live-attenuated vaccines
activates all phases of immune system
provides more durable immunity
low cost
quick immunity
risks of live-attenuated vaccines
secondary mutations can cause reversion to virulence
can cause severe complications in immune compromised patients
some can be difficult to transport due to requirement to maintain conditions like temperature
OAS: antigenic imprinting
original antigen sin - phenomenon where the immune systems first exposure to a virus strongly influences how it responds to related but slightly different strains later
basically immune memory
good as fast response is virus is similar, and memory response can limit disease severity
bad - weaker or mismatched response to new variants and can hinder formation of new variant specific antibodies
pathogen related challenges in vaccine design
high mutation rates - escape immunity
antigenic variability - makes it hard for universal vaccine design
complex life cycles - multiple life stages with different antigens
immune evasion - pathogens hiding from immune system or suppressing it
host immune system challenges in vaccine design
OAS - immune system may prefer old response even when less effective
immunosenescence - older individuals often have weaker immune response to vaccines
immune variability - genetic, age, health, environment influence how people respond to vaccines
technical and manufacturing challenges in vaccine design
choosing the right antigen that will produce a strong long lasting response - difficult
adjuvant selection - tricky to pick right one
delivery method - different routes have different benefits and risks
scaling up - making enough safe effective doses quickly is really hard
public health and social challenges in vaccine design
vaccine hesitant - misinformation or distrust in vaccines can reduce uptake
cold chain requirements - some vaccines require ultra-cold storage - hard in some countries
global access and equity - ensuring low income countries get timely access is a major issue
