Viral Vaccines Flashcards
what is the herd immunity goal in Canada for measles?
95%
how does immune memory impact protection following vaccination?
without vaccination: second exposure
- if long incubation period: long enough for Ab response to mount
- if short incubation period: too fast for an Ab response to mount
vaccination: second expsosure
- life long protective Ab levels –> incubation time is practically irrelevent - Ab is already present
is the SARS-Cov2 vaccine effective?
saved an estimated 20 million lives during its first year
what are some indirect benefits of the covid vaccine?
not having a vaccine yet –> interruptions in medical care –> many cancers not being diagnosed in a timely manner
vaccine = eases the healthcare system
what are 6 common components of vaccines? describe each
- active ingredients: viral or bacterial Ags that directly stimulate the immune system but cannot cause disease
- adjuvants: aluminum salts in small quantities that help to boost the immune response to the vaccine
- abx: prevent contamination by bacteria during the vaccine manufacturing process
- stabilizers: sugar/gelatin keep the vaccine effective until it is administered to a patient
- preservatives: thimersol prevents dangerous bacterial or fungal contamination (only used for influenza vaccines)
- trace components: residual inactivating ingredients such as formaldehyde, and residual cell culture materia (present in small quantities that do not pose a safety concern)
what are 6 approaches to viral vaccine development? what are 8 drug admin routes?
viral vaccine
- live attenuated
- whole inactivated
- VLPs
- recombinant viral vectors
- recombinant subunits
- DNA or RNA
drug admin routes
- otic
- nasal
- rectal/vaginal
- injections
- ocular
- oral
- inhalational
- topical/transdermal
what 6 factors will determine if the technology will “work” outside of the lab?
- scale-up speed
- admin route
- number of doses
- development speed
- storage temperature
- facility of production
what disease was the first live attenuated vaccine used for?
smallpox
describe the basic biology of measles morbillivirus (MeV). why target MeV?
biology
- -ssRNA, linear, env
- uses fusion protein to bind to SLAM to enter cells, buds out of cells
why target
- R0 = 12-18
- severe complication in children and adults: hospitalization, pneumonia, encephalitis, death, complications during pregnancy
how was the MMR vaccine developed, specifically the measles aspect? how did this affect the vaccine strain? what are some characterisitcs of the non-active part of the vaccine?
- MeV tropism restricted to humans and primates using CD46 receptor
- MeV was isolated from a patient and passaged in chicken embryo fibroblasts (CEFs) –> basis for vaccine
- CEFs lack CD46 –> virus adapts to new host environment, hence becoming attenuated towards human cellular environment (most mutations on F and H proteins)
- this results in attentuated MeV having a potentially higher tropism than WT, but less virulence
- MMR is lyophilized = stable; must be stored at 4C; unadjuvanted
what was a whole inactivated vaccine first used against?
typhoid
describe the inactivated polio vaccine (salk vaccine)
- inactivated (formalin) poliovirus strains of all three poliovirus types
- cannot replicate, may need higher and/or more frequent doses, coupled to adjuvants to increase immune reactivity
- requires 4C storage
what is a major drawback of live attenuated vaccines?
possibility of reverting to WT
what was a VLP vaccine first used against?
HBV
how was the VLP vaccine for HPV developed? what are non-active components?
- generated through yeast-based expression system of capsid L1 protein –> self-assembles into VLPs
- vaccine requires 4C storage, uses aluminum as adjuvant
what was a recombinant subunit vaccine first used against?
anthrax
Describe the mRNA vaccine for SARS CoV 2
lipid nanoparticle contains 4 types of lipids
- ionizable cationic lipids: promote self assembly and allows delivery of mRNA to the cytoplasm
- lipid-linked polyethylene glycol (PEG): increases half-life of formulations
- cholesterol: stabilizing agent
- phospholipids: structural support
mRNA coding for spike protein
- uridine modified to pseudouridine for increased stability and decreased anti-RNA immunity
- spike mRNA delivery into cells permites intracellular translocation and processing of spike Ag and loading onto MHC-I and secretion/uptake by APCs and loading onto MHC-II
vaccine is unadjuvanted and requires 4C storage
describe the subunit vaccine for sars cov 2
- matrix-M adjuvant is “proprietary” – made from saponins in soapbark tree
- PS80 nanoparticle core consists of hydrocarbon tail (oleic acid) attatched to a sugar like molecule (sorbitan) to which are attatched short chains of ethylene oxide –> mimics a cell “membrane” that spike inserts into
- required 4C storage
what was a recombinant viral vector first used against?
ebola (rVSV-ZEBOV)
describe the basic biology of ebola virus
-ssRNA, env
describe the ebola vaccine - how it works, safety considerations and other non-active components
replace VSV glycoprotein with ebolavirus glycoprotein
- VSV is a liver, replicating virus capable of infecting various ruminants causing blistering lesions in the mouth
- can infect and cause mild flu symtpoms in humans
- unadjuvanted, requires ulta cold storage (-60C t0 -80C)
