IC10 Types of Vaccines, Components Flashcards
What are the 4 levels of vaccines?
Level 1: individual protection
Level 2: vaccines against communicable disease, protect indiv + create herd immunity
Level 3: global prevention
Level 4: successful vaccination programs, achieve global eradication, protect current popln + future generation
What is cold chain, and why is it important?
Cold chain - temperature controlled supply chain from manufacturer to supplier to provider to administration
- Temp should be b/w 2-8dc
- Insulated container for transportation
- Cold chain monitors - e.g., tracker or label markers that can change color
- Shake test
Why important? - vaccines consist biological materials such as proteins, lipids, carbohydrates, nucleic acid => can be inactivated if frozen or if above 8dc
What is the shake test?
If test vial is NOT frozen, how would it look like compared to the frozen vial?
Shake test is to check whether freeze-sensitive vaccines have been frozen and damaged
How is it conducted?
Frozen control vial: should be from same type and same batch number, freeze and then thaw
Test vial: vial that we suspect is frozen
Shake the control and test vial vigorously for 10-15s, allow vials to rest by placing on table side by side
Freeze-sensitive vaccine in control vial should form flakes that quickly settle to the bottom to form a sediment (*speed at which flakes settle is known as sedimentation rate)
Vial that is not frozen will appear as uniformly cloudy liquid
Compare the vials, observe difference in sedimentation rates for a max of 30min
=> If test vial has SLOWER SEDIMENTATION RATE, then it is probably not frozen and is safe to use
What is ultra-cold storage? What products can be stored in this environment?
Storage down to -80dc can be used for some vaccines to extend storage life (e.g., Ebola, Covid19)
Lyophilized products can be stored down to -25dc (since no liquid component)
Diluents should never be frozen
What are the 6 types of vaccines?
- Inactivated vaccines
- Live-attenuated vaccines
- Subunit, recombinant, polysaccharide, and conjugate vaccines
- Toxoid vaccines
- Viral vector vaccines
- mRNA vaccines
What does inactivated vaccines contain?
Bacteria or virus that have been inactivated by heat or chemical (e.g., formaldehyde)
e.g., influenza, polio, hep A, rabies, tickborne encephalitis, japanese encephalitis
Live-attenuated vaccines use weakened live virus that maintain antigenicity but lose pathogenicity. How are viruses weakened?
Force virus to grow in unusual conditions (e.g., pass through tissue culture in which it replicates poorly), overtime genetic code changes and virus becomes harmless enough to use as vaccine
E.g., MMR, Varicella, yellow fever, rotavirus, cholera
Between inactivated and live-attenuated vaccine,
1. Which is safer?
2. Which induces stronger immune response?
- Inactivated is safer since virus cannot replicate in the body, while live-attenuated may pose risk of uncontrolled replication of the pathogen that can cause the disease
- Live-attenuated induce stronger long-lasting immune response, only need 1 dose, whereas inactivated vaccine may required repeated/multiple doses
*Also note live-attenuated vaccines need refrigeration, harder to store and transport
In which 3 populations might live-attenuated vaccines be a precaution?
- Immunocompromised, on immunosuppressions
- E.g., hematologic or solid organ malignancies, chemotherapy, HIV CD4 <200
- Risk of uncontrolled replication, full blown disease - Pregnant women
- Risk of fetal infection - Infant <1yo
- May still retain antibodies from mother that can cause vaccine to be ineffective (passive immunity from mother)
What are subunit, recombinant, polysaccharide and conjugate vaccines?
They are vaccines that contain a specific part of the pathogen
e.g., spike protein isolated from the virus, polysaccharide from bacterial cell wall
Recombinant vaccine: antigen secreted by host cell in which gene encoding the specific antigen has been inserted into => protein is formulated and administered
E.g.,
- Influenza
- Hep B (surface antigen protein)
- HPV (VLP)
- Typhoid (bacterial cell wall polysaccharide)
- Live oral typhoid (modified strain of the virus)
- Meningococcal (bacterial polysaccharide, conjugated)
- Pertussis (protein antigen)
- Pneumococcus
What are the advantages of using subunit, recombinant, polysaccharide and conjugate vaccines?
- Safe to use in ppl with weakened immune system as it cannot replicate and cause disease (only live virus, or viral genetic code can replicate)
- Low risk of adverse reaction
- May not need refrigeration
What are toxoid vaccines?
Toxoid - altered form of toxins
Toxoid no longer possess toxic effects as exotoxins and endotoxins are removed using formaldehyde, at a certain temp for a period of time (heat + chemical inactivation)
Toxoid vaccines stimulate production of antitoxoid antibodies
E.g., Diphtheria, tetanus
Is the immune response induced by toxoid vaccines high?
No, usually need booster dose
May also need adjuvant to boost immune response
Describe any concerns for the detoxification process of toxins for toxoid vaccines.
Detoxification process must be well controlled, epitope of the antigen cannot be excessively disrupted
How do viral vector vaccines work?
Genetic material inserted into inactive and harmless viral vector, viral vector injected and enters human cell to produce spike protein
*Viral vector will be degraded after a few days, viral vector is incapable of causing any disease
What are the storage requirements for viral vaccine?
Cold storage
Stability is an issue
How do mRNA vaccines gain entry into cells?
mRNA surrounded by tiny lipids (capsid) that will help mRNA enter cells
E.g., formulate with:
- cationic/ionizable lipids
- PEG lipids
- neutral/anionic ilpids
- cholesterol
*these ensure good stability + structural plasticity + enhanced gene delivery
What are the basic components in a vaccine?
immune antigen
suspension fluid
preservative
stabilizer
surfactant/emulsifier
adjuvant
can also have:
trace components - e.g., small amount of residual ingredients such as formaldehyde
antibiotic to prevent contamination
What is the purpose of preservatives?
Ensure vaccine content and potency remain unchangeed, prevent bacterial and fungal growth (in multi dose vials)
What excipients are used as preservatives?
Formaldehyde: kill or inactivate unwanted germs
- 37% solution
- 10%: formalin
- pungent smell
2-Phenoxyethanol:
- used in cosmetics and topical formulations
- narrow range of action, can be used in combination with parabens
- easily eliminated with little toxicity
- antibacterial activity against gram negatives (e.g., pseudomonas, proteus)
Thimerosal:
- used in parenteral formulations
- used as alternative to benzalkonium chloride and other phenylmercuric preservatives
- bacteriostatic and fungistatic
- stable at normal temp and pressure, but exposure to light may cause discoloration
- possible hypersensitivity (phase out)
What are adjuvants? What are the 2 types of adjuvants?
Adjuvants are added to antigen to induce more potent immune response
- Vaccine delivery system - microparticles and nanoparticles that help to concentrate and target the antigen
- Immunostimulatory adjuvants - immunopotentiators that help activate the immune system (through cytokines or through pattern recognition receptors)
What are the more commonly used adjuvants?
- Alum salts (aluminium phosphate, aluminium hydroxide)
- weak effect but slow down rate of release of the antigen, and also incr the duration of antigen interaction with the immune system
=> Vaccine delivery - MF59 (used in influenza vaccine)
- submicron o/w emulsion containing squalene
=> immunostimulatory
Other adjuvants have side effects that make them under evaluated:
Complete Freund’s adjuvant (heat killed mycobacteria suspended in oil) - can cause inflammation
Incomplete Freund’s adjuvant (w/o emulsion of non-metabolizable oils) - cutaneous reaction
Emulsions (w/o and o/w) generally considered toxic and dangerous to use
Montanide (oil-based adjuvants) - experimental in animals
What are some examples of biological adjuvant? (to stimulate immune system)
Cholera toxin
LPS
Pertussis toxin (PT)
Toxin A and B of C. difficile
Staphylococcal enterotoxin
Proteosomes (meningococcal outer membrane protein)
Vaccine delivery vehicle:
Liposomes (lipid layers that encapsulate antigens)
