Unit 8: Vaccinology Flashcards
what is the hallmark of a successful vaccine?
a vaccine that induces an immune response which is disease preventing, long-lasting, ideally sterilising
provides a broad protection against all serotypes of a pathogen
what should a vaccine be?
- safe
- affordable
- easy to administer
- long shelf life + temp tolerant
- DIVA compliant
what is DIVA?
differentiating infected from vaccinated animals
what are some of the types of vaccine?
- whole organism vaccines (killed/inactivated vs live attenuated)
- toxoid
- subunit
- viral vector
- nucleic acid
give some examples of killed/inactivated whole organism vaccines
- rabies
- hepatitis A
- (inactivated) polio
what are the pros and cons of killed/inactivated whole organism vaccines?
- can’t replicate
- simple + stable
- shorter length immuno-protection
- need for boosters
give some examples of live attenuated whole organism vaccines
- MMR
- intranasal influenza
- BCG
what are the pros and cons of live attenuated whole organism vaccines?
- strong + long lasting immune response
- simple
- disease reversion possible
- temperature sensitive
give some examples of toxoid vaccines
- diptheria
- tetanus
what are the pros and cons of toxoid vaccines?
- memory developed after first injection
- strong immune response
- only effective if disease caused solely by bacterial endotoxins
- requires cold chain
give some examples of subunit vaccines
- HPV
- hepatitis B
- meningococcal bacteria
what are the pros and cons of subunit vaccines?
- no live components
- relatively stable
- complex and time consuming
- low immunogenicity needing adjuvants + boosters
give some examples of viral vector vaccines
- ebola
- SARS-CoV2
- canine distemper
what are the pros and cons of viral vector vaccines?
- strong immune response (T/B response)
- no disease risk
- previous exposure could reduce effectiveness
- complex
what is different about nucleic acid vaccines?
- DNA delivered to nucleus of target cells (electroporation)
- mRNA needs protection from degradation + use of lipid membrane
- mRNA translation lasts few days then naturally broken down
- mRNA moderna/pfizer vaccine
what are the pros and cons of nucleic acid vaccines?
- no infection risk
- simple, cost effective + heat stable
- only protein antigens can be expressed
- potential atypical protein processing
- potential integration of foreign DNA into genome
what T cell response do vaccinations induce?
CD4+ T cell = Th2 response
what are some factors to consider when deciding vaccine delivery methods?
- size, shape, charge, hydrophobia, receptor interacting surfaces of antigens
- vaccine type
- use of + type of adjuvant
- presence of repetitive structures?
what are some host factors that could lead to vaccine failure?
- age influence
- immunodeficiencies
- waning immunity
- immunological interference
what are some vaccine factors that could lead to vaccine failure?
- lack of immune response required for protection
- incomplete coverage of strains
- vaccine escape mutants
- antigenic interference
- manufacture/ storage issues
what is a LNP?
lipid-based nanoparticles - used for self-assembly in mRNA vaccines
how is the efficacy of viruses defined?
the measure of how much a vaccine has lowered a risk of getting sick with that pathogen
what are some pros and cons of mRNA vaccines?
- easy, rapid, safe with high efficacy
- CD4+ + CD8+ immune response + antibodies
- short half life
- high cost, complex delivery and cold chain dependent
- strong immunogenicity (ssRNA)
what are the top 5 most deadliest human diseases?
- tuberculosis (10mil, 1.5mil deaths)
- measles (140,000 deaths)
- malaria (228mil, >405,000 deaths)
- influenza (3-5mil, 650,000 deaths)
- diarrhoeal diseases (525,000 deaths)
covid at 6 with >6.8mil deaths over 3 years
why is it difficult to vaccinate against parasites eg plasmodium?
- different protein expression at different points of the life cycle
- large/ complex genome with immune evasion mechanisms
- intracellular niches
- antigen polymorphisms
- redundant host cell invasion pathways
- immune suppression
what can you vaccines target at different stages of plasmodium infection?
- gamete targeting within mosquito= block transmission
- blood stage = no MHC = antibodies, CD4+ T cells, macrophages and complement
- pre-erythrocytic = MHCI = antibodies, CD4+, CD8+, macrophages
what does the RTS,S/AS01E vaccine for malaria target?
CSP (circumsporozoite protein)
basically is the hepB vaccine - recombinant CSP fused to HepBV surface antigen
is a yeast vaccine
what was the problem with the RTS,S/AS01E vaccine? how was it improved?
very poor efficiacy - 36%
BUT did prevent 1774 malaria episodes per 1000 children
efficacy drops after 6 months
additional use of matrix M in vaccine = 77% efficacy + yeast changed
why? can gametocyte + gamete surface proteins be targeted as a vaccine option?
antibody response will inhibit fertilization = no disease transmission
what cells of the immune system help prevent constant inflamed gut?
- M-cells = above Peyer’s patches, stimulate IgA/G
- yS T cells
- regulatory T cells
why use yeast as a vesicle for oral vaccines?
- cheap
- safe
- common in diet and available in many forms
how does Dectin-1 and TLR2 initiate the immune system to yeast antigens?
Dectin-1 = uptake of antigen + production of ROS, expressed on M-cells
TLR2 = production of inflammatory mediators as antigen response
what is the molecular basis for attenuation in the BCG vaccine?
RD1 (region of deletion) during attenuation = loss of ESAT-6 secretion system 1 (ESX-1) = no secretion of major protein antigens
what are some strategies for assessing vaccine efficacy?
- lab based = measure immune respose = IFNy-ELISA
- measure protection against in vivo models via pathology scores/ bacterial load
- population = randomised controlled + observational studies
why does the BCG vaccine need to be improved?
- limited efficacy against pulmonary TB in adults
- only 50% protective efficacy in children
- doesn’t protect against disease in people already infected etc
how can antigen presentation be improved in BCG vaccine?
- express listeriolysin O = phagosomal membrane perforation = in cytosol = more anitgen presentation
- deletion of urease C = no ammonia produced = acidic environment = improved listeriolysin O
