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PHS2104 > Lecture 5: Vaccines and RNA drugs > Flashcards

Lecture 5: Vaccines and RNA drugs Flashcards

1
Q

What are the common components of vaccines?

A
  1. Active ingredients: viral or bacterial antigens that directly stimulate the immune system but cannot cause disease
  2. Adjuvants: Aluminium salts in small quantities that help to boost the immune response to the vaccine
  3. Stabilizers
  4. Preservatives
  5. Antibiotics
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2
Q

Why are particulate antigens more immunogenic than soluble ones?

A

Because they are more easily phagocytosed

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3
Q

How do vaccines work?

A
  1. Vaccines mimic natural infection by establishing pathogen-specific immunologic memory in vaccinated individuals.
  2. When re-exposed to the pathogen, a rapid, robust response is mounted in vaccinated individuals because of existing memory B cells (and T cells) that recognize the pathogen.
  3. This way, the host remains free from the disease, and if a vaccinated individual does develop the disease vaccinated against, the disease is likely to be of a milder severity than without vaccination.
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4
Q

What are the different types of vaccines?

A
  1. Whole microbe vaccine
  2. Subunit vaccine (using parts that trigger the immune system)
  3. RNA vaccine
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5
Q

What kind of whole microbe vaccines are available?

A
  1. Inactivated vaccine
  2. Live-attenuated vaccine
  3. Viral vector vaccine
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6
Q

What kind of subunit vaccines are available?

A
  1. Subunit only
  2. Virus like particle
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7
Q

What are inactivated vaccines composed of?

A

Composed of viruses or bacteria that have been rendered non-infectious, typically by chemical (e.g. formaldehyde, glutaraldehyde) or physical processes such as heat.
They are administered together with an adjuvant to increase potency

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8
Q

What are the disadvantages of inactivated vaccines?

A
  1. Less immunogenic than live vaccines.
  2. Little or no cell-mediated immunity induced because they don’t infect the cells
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9
Q

What are live attenuated vaccines composed of?

A
  1. Composed of weakened forms of viruses or bacteria.
  2. Reduced virulence (ability to cause disease) while retaining the ability to stimulate an immune response.
  3. Can replicate within the body, leading to a robust and long-lasting immune response.
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10
Q

How are live attenuated viruses generated?

A

Generated through serial passage, involving the repeated passage of the pathogen through cell cultures or animals (non-natural hosts) to adapt and attenuate its virulence.

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11
Q

What are the disadvantages of live attenuated vaccines?

A
  1. Risk of reversion to virulent form.
  2. So, it’s not recommended for individuals with weakened immune systems and pregnant women.
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12
Q

What are viral vector vaccines composed of?

A
  1. Use of a harmless virus (viral vector) to deliver immunogenic proteins from a pathogenic microbe.
  2. Engineered to carry genetic instructions (RNA or DNA) for making
    immunogenic subunits of the pathogen
  3. The harmless virus serves as a platform or vector to deliver the protein into the body
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13
Q

What are the advantages of vector vaccines?

A

Provides strong and durable immunity.
* Mimics natural infection.
* Possibility of expressing multiple antigens

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14
Q

What are the disadvantages of vector vaccines?

A

Vector vaccines may have disadvantages due to the potential integration of vaccine DNA into the host’s genome and the development of host-induced neutralizing antibodies against the vector carrier.

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15
Q

What is an example of a viral vector vaccine?

A

Influenza vaccine

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16
Q

What are subunit vaccines composed of, and how are they produced?

A

Composed of immunogenic protein antigens derived from pathogens.
Produced using genetic engineering techniques, where the genes encoding the desired antigens are inserted into a host cells (e.g. yeast or CHO cells).

(Dependent on the knowledge of which antigen(s) is/are most immunogenic)

17
Q

What are the advantages of subunit vaccines?

A
  1. Safety: No live or inactivated pathogens.
  2. Precision: Targeted immune response against specific antigens.
  3. Flexibility: Potential for combining multiple antigens for broader protection
18
Q

What are the disadvantages of subunit vaccines?

A
  1. Require adjuvants (e.g. aluminum salts) to enhance immune stimulation.
  2. Require booster doses to prolong immunity
19
Q

What are virus like particle vaccines composed of ?

A
  1. Composed of the outer shell or capsid structure of a virus.
  2. It mimics the structure of viruses without containing the viral genetic material necessary for replication.
  3. Non-infectious (safe)
20
Q

How are virus like particles produced?

A
  1. Incorporate the different subunits of the viral capsid protein into different vectors
  2. Co transfect them in the optimal molar ratio into mammalian cells (CHO?)
  3. The proteins get translated and they assemble into virus capsids and are extracted from these cells.
21
Q

What are mRNA vaccines composed of ?

A
  1. Composed of messenger RNA (mRNA) that instruct cells in the body to produce immunogenic proteins from a pathogen.
  2. Synthetic protein coding mRNA with modified nucleosides to enhance stability and increase efficacy
  3. The mRNA is delivered through lipid nanoparticles, which protects the mRNA from degradation, and facilitates cellular uptake
22
Q

Why is mRNA a better option than DNA in vaccines?

A
  1. mRNA is non integrative unlike DNA
  2. Safe: Not inherited by daughter cells –> no risk of integrating into or modifying the host genome
23
Q

What is the process by which an mRNA vaccine leads to an immune response in the body?

A
  1. Nanoparticles deliver mRNA into cells at the injection site.
  2. mRNA are translated into protein antigens in the cell.
  3. Antigens are expressed or presented on the cells.
  4. B and T cells activation.
24
Q

How are mRNA vaccines produced and what are the advantages of it’s production?

A

Produced through in vitro transcription.
Advantages:
1. Rapid, inexpensive and scalable manufacturing
2. High yields of in vitro transcription reactions.
3. Flexible, can be adapted to encode any antigen in response to emerging infectious diseases.

25
Q

What are the disadvantages of mRNA vaccines?

A
  1. Low immunogenicity
    * Require booster doses to prolong immunity.
    * Require adjuvants to enhance immune stimulation
  2. Poor stability of mRNA
    * Subjected to degradation by extracellular RNAses, which are found everywhere in the body.
    * Can be recognize by innate immune cells and cleared (so it needs to be modified to make it less recognisable)
    * Requires cold storage
26
Q

How is the open reading frame in mRNA vaccines modified and why?

A
  1. Uridine bases are replaced with pseudouridine
  2. This prevents the mRNA from being recognised and degraded
    - Enhance mRNA stability and potency and reduce immunogenicity
  3. The sequence/codons are optimised to increase translational efficiency
27
Q

How is the 5’capping in mRNA vaccines modified and why?

A

The Cap structure is changed to enhance mRNA stability and increase translational efficiency.

28
Q

How is the poly-A-tail in mRNA vaccines modified and why?

A

The tail is elongated to enhance mRNA stability and increase translation efficiency

29
Q

How are the untranslated regions in mRNA vaccines modified and why?

A

Their length and structure is modified to increase translation efficiency

30
Q

How do RNA amplifying vaccines work?

A
  1. They contain a type of RNA that can replicate and amplify itself within host cells, enhancing the production of the encoded protein.
  2. Based on an alphavirus genome, where the genes encoding the RNA replication machinery are intact but the genes encoding the structural proteins are replaced with the antigen of interest.
  3. Enables a large amount of antigen production from an extremely small dose of vaccine
31
Q

How do cancer vaccines work?

A
  1. They stimulate the immune system to recognize and eliminate cancer cells
  2. The antigens are taken in by APCs which present the antigen to CD8/CD4 T cells, which are now able to recognize tumor specific antigens which allows them to bind to an kill cancer cells
32
Q

What is the target of previous and current cancer vaccines?

A
  1. Previous vaccines: Target well-known tumor-associated antigens (antigens that are upregulated in cancer cells, present in healthy cells at low levels).
  2. Current vaccines: Target Neoantigens (tumor-specific antigens generated by mutations in tumor cells)
33
Q

What are the advantages of cancer vaccines?

A
  1. Precision: Target specific mutations unique to the individual’s cancer.
  2. Reduced Toxicity: Minimizes damage to healthy cells.
  3. Immunogenicity: Triggers a robust and targeted immune response
34
Q

What are the disadvantages of cancer vaccines?

A
  1. Tumor Heterogeneity: Addressing the diversity of mutations within a tumor.
  2. Immune Evasion Mechanisms: Strategies employed by cancer cells to evade immune detection.

PHS2104 (15 decks)

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