W14 Vaccine types (GN) Flashcards
What are the 3 Types of vaccination?
-
Whole organisms
-Live attenuated vaccines
-Killed/inactivated vaccines -
Purified macromolecules (Partial microorganism)
-Subunit/Recombinant Protein Vaccines
-Toxoid Vaccines
-Polysaccharidic or protein-conjugated Vaccines -
Nucleic acid vaccines
-DNA vaccines
-mRNA vaccines
What is a Live attenuated vaccine?
Containing whole bacteria or viruses which have been “weakened”(attenuated)
-Genetically altered microbes with reduced virulence but retain their immunogenicity
-Genes encoding virulence factors are deleted or mutated
What are the advantages of a live attenuated vaccine? (4)
✓Follow a natural infection
✓Elicit a strong cellular and antibody response
✓Long-lasting response
✓One or two doses required
What are the disadvantages of a live attenuated vaccine?
- Live microbes can mutate and revert back to a virulent form → causing mild disease (rare)
- Attenuated forms can cause disease in immunocompromised patients and unborn babies
-Contraindicated in immunocompromised or pregnant women - They require refrigeration to be active → heat and light can inactive the microbes
-difficult to be shipped and stored in developing countries
Examples of live attenuated vaccines?
➢ measles, mumps and rubella (MMR), chickenpox, poliovirus, rotavirus,
nasal flu vaccines → Replicating viruses
➢ Bacillus Calmette Guérin (BCG) vaccine → Replicating bacteria
➢ Smallpox vaccine → Live non-replicating virus
What is a Killed/inactivated vaccine?
Inactivated microorganisms.
Containing whole bacteria or viruses which
have been killed/inactivated
-Microorganisms are grown in culture media and killed by heat or chemical agents (e.g. formalin)
* Microbes cannot replicate or cause disease, without comprising antigenicity
What are the advantages of a kill/inactivated vaccine? (2)
Advantages
✓Safer for immunodeficient patients and in pregnancy than live vaccines
✓More stable than live vaccines → no requirements of refrigeration
-can be shipped to developing countries as freeze-dried form
What are the disadvantages of a kill/inactivated vaccine?
Weaker response than live microorganisms → multiple doses are required for long-term immunity
▪ A first dose primes the immune system, while boosters develop a protective immunity
▪ Adjuvants are CRITICAL for enhancing the response
▪ They may fail to develop immunity in
immunocompromised patients
What are examples of killed/inactivated vaccines?
➢ Polio, Hepatitis A, flu and rabies vaccines → viruses
➢ Pertussis, cholera, meningococcal vaccines → bacteria
Live attenuated versus inactivated vaccines
Production:
L- Cell culturing system under adverse conditions to select avirulent microorganisms.
Or genetical alteration
I- Culture and inactivation of microorganisms by chemicals/radiations
Booster requirement:
L- Usually, only a single booster
I- Multiple booster
Stability
L- Less stable
I- Stable
Immunity induced
L-Humoral and cell-mediated
I- Mainly humoral
Genetical reversion tendency:
L- May revert to virulent form
I- No risk
Subunit vaccines (microbial components)
What do they contain?
How are they produced?
Examples? (3)
- Contain only antigenic molecules of microbes. Not the whole organism.
- Produced by fractionating microbes into components or by recombinant DNA technology and purified
- Components are selected as capable of stimulating a
specific immune response and protect from relevant
pathogen infection and/or related severe disease
Subunit vaccines (microbial components)
➢A) Protein/peptide vaccines
➢B) Toxoid
➢C) Polysaccharidic conjugates
What are the advantages of subunit vaccines?(microbial protein)
✓Safe for immunodeficient patients
✓Less likely to induce side effects
What are the disadvantages of subunit vaccines?(microbial protein)
- Poor immunogenicity →Antigens may not retain their original 3-D conformation in the microbes
- Require boosting doses
- More challenging and expensive to develop
Subunit vaccines – A) Protein vaccines
What do they consist of?
Examples?
- Consisting of protein/peptide antigen(s) including
epitope(s) that antibodies or T cells recognise →
triggering a specific strong immune response
➢ E.g. external viral proteins (envelope or capsid proteins)
* Can contain 1 to 20 antigens.
Hepatitis B vaccine, MenB Vaccine (Meningococcal B Vaccine)
Subunit vaccines – B) Toxoid vaccines
Examples?
- Against bacteria producing exotoxins, responsible for a disease (C. tetani)
-Soluble and heat-labile proteins released outside by viable bacteria (Gram +ve and -ve) - Toxoids are toxins produced in culture systems and detoxified to produce harmless vaccines that prime the immune system to inactivate the bacterial toxin
Diphtheria and tetanus vaccines → bacteria
Subunit vaccines – B) Toxoid vaccines
Advantages and disadvantages?
Advantages - Highly efficient and safe immunized agents (immunodeficient patients and in pregnancy) and no risk of mutations
Disadvantages - Require many boosters
Subunit vaccines – C) Polysaccharidic conjugate
What are they produced against?
Produced against capsulated pathogenic bacteria
▪ S. pneumoniae (pneumococcus), N. meningitidis (meningococcus),
- Include the surface polysaccharide (usually low
immunogenic) on the capsule of pathogenic bacteria - Attached to a toxoid protein to creates a strong
immune response → Conjugate
Subunit vaccines – C) Polysaccharidic conjugate
Adv and Disadv?
Examples?
➢ Long-lasting immunity
➢Capsule polysaccharides are bacterial type-specific (require more polysaccharides to extend coverage to a bacterial species
✓ Hib/MenC vaccine (even alone) → Haemophilus influenzae type B capsular polysaccharide +
meningococcal capsule polysaccharide (group C) both directly conjugated to tetanus toxoid
✓ Children’s pneumococcal vaccine against Streptococcus pneumoniae → polysaccharides
from the surface of the 13 most common invasive bacterial types conjugated to tetanus toxoid
Nucleic acid vaccines
Based on the principles of gene expression
* Design of antigen-coding DNA sequence (genetically engineered)
* Delivery inside human cells
* Exploiting the cellular machinery (transcription → translation) to produce viral proteins → antigens
mRNA vaccines: Nucleic acid vaccines
- Delivery of DNA vaccines inside cells
- Delivery of mRNA vaccines inside cells
A) mRNA vaccines
What are they based on?
MOA?
Based on synthetic RNA coding for microbial
antigenic protein (coronavirus spike proteins like
in the RNA vaccines against SARS-CoV-2 from
Pfizer and Moderna)
- RNA enters cell cytoplasm (site of translation)
- Translation produces coronavirus spike proteins
- Spikes are presented outside the cell membrane
to activate immune system
B) DNA vaccines
What are they based on?
MOA?
- DNA vaccines can be uptake by cells
- A small portion (0.1%) reaches the nucleus
- DNA is transcribed into mRNA and translated
into antigenic proteins - Antigenic proteins are detected by the immune
system → humoral and cell-based response
Plasmids including a gene encoding the microbial antigen
Vaccine antibody response to spike within 1 week
Nucleic acid vaccines
What are the advantages? (3)
➢ Cheap and quick to make
➢ Cheap and quick to make
➢ Safe and effective to stimulate both humoral and cell-based immunity
Nucleic acid vaccines
What are the disadvantages? (4)
➢ Low stability of mRNA vaccines, requiring low storage temperatures
➢ Individual variability (long-term effects)
➢ Intracellular delivery challenges
➢ Public hesitancy based on misconceptions