WEEK 9 - Vaccine Delivery Flashcards
What are viral vaccines
Deliberate exposure to disease-causing virus to induce protective host immune response WITHOUT experiencing the full infection
- immune system produces memory B and T cells
- very selective antibodies produced ~ specifc to certain epitotes
- high affinity
Can be achieved by exposure to:
1. Killed / inactivated vaccine
- exposure to all componets of virus
2. Weakened / live attenuated vaccine
3. Antigenic elements of virus / subunit vaccine
- exposure to parts of virus e.g. spike proteins
- produce antigen presenting cells
What is required for optimal vaccine delivery
- Preserve vaccine immunogenic activity
- Preferably low dose & low dosing frequency
- Targeting/localization
- Does NOT trigger undesired immune/allergic responses
- Protect antigenic cargo (storage, supply & physiological environment)
- Enhance cellular uptake of antigenic cargo
- Help present the viral antigen in an effective and sustained manner
List the 7 types of viral vaccines
- Inactivated (killed) Vaccine
- Live attenuated (weakened) vaccine
- Replicating viral vector vaccine
- Non-replicating viral vector vaccine
- Subunit Vaccine (non-viral)
- DNA Vaccine
- RNA Vaccine (non-viral)
Inactivated (killed) Vaccine
Viral Vaccine
Contains WHOLE virus paricles which have been killed by heat or chemical to prevent them causing infection
- still conatins viral components
- Safest vaccine as virus is inactivated
- useful in elderly, babies, immunocompromised - ISSUE: does NOT elicit STRONG IMMUNE RESPONSE / long-lasting immunity
- requires booster doses
e.g. Polio, COVID
Live Attenuated (weakened) Vaccine
Viral vaccine
Contains live virus particles that have been WEAKENED to prevent them causing disease
- Not suitable for immunocompromised people as may cause disease
- Elicit a STRONG IMMUNE RESPONSE = long-lasting immunity
e.g. MMR, COVID, flu, chickenpox
What are viral vectors
NOTE: A type of viral vaccine
Vectors based on viral particles, used for delivery of drugs, vaccines or gene therapy
- Deliver genetic material into host cell
- There are 2 types (replicating and non-replicating)
- Currently only have 6 viral vectors due to immunogeneicty + safety concerns (DNA)
Replicating viral vector vaccine
Viral vaccine
Alter a low pathogenic virus into a replicating viral vector
- low pathogenic = doesn’t normally cause disease
- Alter viral vector genetic material = low pathogenic virus encodes antigens of a disease-causing virus
- Vector replicates inside host = producing more of itself
- Elicits STRONG IMMUNE RESPONSE
- BUT may NOT WORK if indiviudal has developed immunity to low pathogenic virus - Mainly used in Vet. medicine not humans
Non-replicating viral vector vaccine
Viral vaccine
Alter a low pathogenic virus into a replicating viral vector
- low pathogenic = doesn’t normally cause disease
- Alter viral vector genetic material = low pathogenic virus encodes antigens of a disease-causing virus
- same process as othe vector but does NOT REPLICATE inside body
- Has better efficacy and safety BUT requires HIGH DOSES
Subunit Vaccine
Non-Viral vaccine
Use antigenic (spike) proteins from disease causing virus
- Safe as no genetic material is used
- Can NOT replicate in body
ISSUE:
- Require multiple dosing for long-lasting immunity
- Require adjuvants
e.g. HPV, COVID
DNA Vaccine
Viral vaccine
Use modified DNA plasmids that have code of viral antigen = antigenic proteins produced
- Host cell uptakes plasmid
- Forms mRNA + replicates
- Leads to expression of viral antigen
Host cell is used to produce APC- APC triggers immune response
Currently NO human DNA vaccine due to weak immune response
RNA Vaccine
Non-Viral vaccine
Use mRNA plasmids that encode virus antigen = antigenic proteins produced
- safe and selective
PROBLEMS:
- Delivery (mRNA is big, lipophilic molecule)
= can easily partition but not easily absorbed
- Trigger unintended immune response e.g allergies
- Can be easily degraded by nucleases
DIFFERENCE BETWEEN DNA / RNA Vaccine:
- RNA vaccine does NOT interfer with host / human DNA
What are the challneges of vaccines
Traditional vs Modern
Traditional (live attenuated / inactivated)
- Elicit immune response via same pathways of original disease
- Risk of severe SE due to unexpected immune responses
Modern (recombinant antigens)
- ↓ risk of SE (as they’re NOT viral particles)
- Elicit specific immune response
- Weaker response = requires adjuvant
- Nucleic acids (DNA/RNA) & subunits have poor stability + can be degraded easily
Adjuvant technologies
What it is, examples, 3 adjuvant classes and SE
Adjuvants - are immunostimulants
- help create a stronger immune response against antigens (spike proteins)
- help the immune system generate antibodies
- USE: inactivated and subunit vaccines
Adjuvant Classes:
1. Active immunostimulant
- adjuvant is given to ↑ immune response
2. Carrier
- carries anitgen + provides T-cell help
3. Vehicle adjuvant
- adjuvaant acts as a matrix for antigen AND is immunostimulant
- e.g. oil emulsions, liposomes
Side Effects:
- Injection site pain, inflammation, necrosis
- Sterile abcess, ulcers
- Systemic reactions: N&V, fever, immunotoxicity, anaphylaxis
Examples of Adjuvants:
- O/W emulsions e.g. lipovant, montaide
- Saponins e.g. QS21
- Aluminium salts
What is the role of adjucant technologies in vaccine formulations
- Improve immunogenicity of antigen / vaccine
- allows weak antigen to be recognised by immune system
- Reduce dose (i.e. multiple dosing) / need for boosters
- Improve efficacy of vaccine in newborns, elderly, immunocompromised
- Can act as delivery systems for antigen = better uptake
What are delivery routes for vaccines
- Intramuscular (IM)
- Has less SE (main SE = pain)
- traditional route - Subcutaneous (SC)
- Local delivery - Transdermal (TD)
- Local delivery (but goes deeper into skin)
- Vaccine can be absorbed into blood vessels = systemic effect - Intranasal (IN)
- Common for flu vaccine
- No injection site SE
- Doesnt require sharps disposal, training - GI
- Not common
- Useful if GI is site of infection
List non-viral aproaches
- Subunit vaccines
- RNA vaccines
- Nanovaccines / nanocarriers
- Advanced delivery systems
- inc. Hydrogels, Microneedles, Physical approaches
List 4 types of Nanovaccines
- Lipid-based Systems
- Nanoparticles (NPs)
- Liposomes - Hybrid Systems
- Virosomes
- Virus-like particles
- Polymer-based Systems
- Inorganic NPs
Lipid-based Systems
Nanovaccines
Includes: Liposomes, Lipid NPs (LNPs), Lipoplex
- some systems e.g. liposomes have adjuvant action
- lipoplex = complex formed between cationic lipids + nucleic acids (mRNA)
- Use amphiphilic lipids to create lipid systems
- lipid core + phospholipid surface - Lipids are biocompatibale, biodegradable
- Lipids have good surface activity
Compositions:
- PEGylated lipids - improve NP proeprties BUT may elicit allergic reactions
- lipids conjugated to PEG
- Cationic lipids
- Phospholipids, Cholesterol - improve NP properties
- Ionisable lipids - facilitae endosomal escape
- LNPs are engulfed by endosome = endocytosis
- lipid helps LNPs escape and be released into cytoplasm
Examples:
- Shingrix (HZ subunit vaccine)
- is an adjuvant, recombinant vaccine
- antigen is loaded into liposome
- lipid bilayer forms sphere shape
Hybrid Systems
Nanovaccines
Includes: Virosomes, Virus-like particles (VLPs)
- Non-replicating, artificial viruses
- composed of liposome covered with viral glycoprotein - Non-infectious, can bind and penetrate host cell = good cellular uptake
- Safe + stable subunit vaccine
Polymer-based Systems
Nanovaccine
Includes: Polymeric NPs, Nanocapsule, Dendrimers, Polyplex
- Polymer systems can be made from natural or synthetic polymers
- Can easily tune properties, molecular design
- Are biocompatiable, biodegradable
- physiological enzymes / pH can degrade them - Have ↓ immunogenecity = avoide undesired immune responses
Polymeric NPs:
- Polymers that form a nanoparticle used to load antigens / antigen delivery
- Polymers with more PLA induced a better immune response
Polyplexes:
- Complex formed between polymer (cationic) and nucleic acid (anionic)
- Uses cationic polymers due to electorstatic attraction
- Polyplexes made of high amounts of PEI can be toxic to host cells (disrupt membrane ~ anionic phospholipid)
Dendrimers:
- Highly branched, 3D star shaped molecule
- Load antigen into core + surface is functionalised with targetting ligands (which bind to receptors)
- Act as adjuvants
Nanocapsules:
- Lipid core stabilised by phospholipids + coated externally with polymer containing antigens (= polymeric shell)
- Can load hydrophobic / lipophilic adjuvant into core
Inorganic Nanoparticles (NPs)
Nanovaccine
Includes: Gold, Iron oxide, Silica NPs
- Used for delievery of DNA and subunit vaccines
- Still in early pre-clinical research
Advantages of Nanovaccines
- Easy to engineer
- ↓ toxicity
- ↓ undesired immunogenecity e.g. allergies
- ↓ costs + can produce at large scale
- Protect antigen from degradation
- Can act as adjuvants (liposome)
- ↑ safety and efficacy
What are the 3 advanced vaccine delivery systems
- Microneedles (MNs)
- Hydrogels
- Electroporation
Microneedles (MNs)
Advanced delivery systems
MNs are small needles insterted into skin
- transdermal delivery = delivery can be uptaken by blood vessels
- dont cause pain as they are small
3 Types of MNs:
1. Coated MNs
- metallic array base is coated with dissolving formulation containing antigens + adjuvants
- Dissolving Formulations
- Entire array is dissolvable = upon delivery needles dispose themselves
- material dissolves in skin + slowly release vaccine - Sustained Release Formulations
- Produce implantable MN tips
- MN tips remian in skin after insertion (needle detaches from backing and stays in skin for a whilw)
- MN tip slowly degrades = sustained release
Hydrogels
Advanced delivery systems
Viscous materials
- can be injectable or sprayable
- Biocompatible (90-95% = water and 5% = polymer) + biodegradable
= safe formulation
- low toxicity - Provide slow, controlled release of antigenic cargo = enhanced APCs = improved immune responce
- Can be used as vehicles
- Can have adjuvants added to them
Hydrogels can be formed in 2 ways:
1. Self-organisation of peptides and proteins
2. Cross-linking of polymers
3.
Electroporation
Advanced delivery systems
A physical method used to aid entery of DNA/RNA into cells
- Use short electric high coltage pulse (generated from hand-held device)
- Creates small pores in cell membrane
List the differences between traditional viral vaccines, recombinant viral vectors and nanovaccines
