L.13 Vaccines Theory and Practise 3 Flashcards

1
Q

What are conjugate vaccines and how do they enhance immune response?

A

Conjugate vaccines enhance immune response by chemically linking capsular polysaccharides to a protein antigen. This conjugation stimulates both T and B cell responses, overcoming the issue of weak T cell activation by polysaccharides alone.

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2
Q

What challenges are faced in developing synthetic peptide vaccines?

A

Synthetic peptide vaccines must include immunodominant B cell epitopes to stimulate memory T cell development. The main challenges include understanding HLA presentation of peptides and the dual nature of peptides as stimulatory or suppressive, as most B cell epitopes are conformational.

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3
Q

What are the advantages and disadvantages of subunit vaccines?

A

Subunit vaccines are safe, carry no risk of infection, and may be easier to store. However, they typically elicit a less powerful immune response compared to live attenuated vaccines and often require repeated vaccinations and adjuvants.

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4
Q

What are adjuvants and how do they work in vaccines?

A

Adjuvants are substances added to vaccines to stimulate the immune system. They can prolong the half-life (aluminium salts) of an immunogen at the injection site or trigger immune system “danger signals.” They can include aluminium salts, oil emulsions, toxoids, and other chemicals.

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5
Q

What are the roles of Toll-like receptors and PAMP/DAMP signals in adjuvant function?

A

Adjuvants can activate the innate immune system by stimulating Toll-like receptors and recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), enhancing the vaccine’s effectiveness.

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6
Q

What are the considerations and potential risks associated with adjuvant use in humans and an example of when this happened?

A

While adjuvants like alum are widely used to enhance immune response, high efficiency may come with risks, such as autoimmunity or chronic inflammation. The long-term effects of adjuvants, such as in the case of the H1N1 vaccine associated with increased incidence of narcolepsy

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7
Q

What is the principle behind DNA vaccines and what are their advantages and challenges?

A

DNA vaccines aim to express pathogen genes transiently within host cells, resembling a natural infection and eliciting T and B cell memory. They are stable and easy to distribute but may produce only a mild immune response and require boosting.

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8
Q

What are the advantages and disadvantages of DNA vaccines?

A
  1. Advantages of DNA vaccines include not requiring complex storage and transportation and being adaptable to widespread vaccination programs with simple delivery methods like the “DNA gun.”
  2. Disadvantages include the potential for a milder immune response compared to live vaccines, often necessitating booster shots. Also To get the DNA into the cells, it’s often encapsulated in lipid carriers there’s a possibility that the lipid-DNA complex could end up in unintended locations potentially leading to an autoimmune response
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9
Q

How do RNA vaccines work and what is their storage advantage?

A

RNA vaccines encode specific antigens and lead to transient expression within cells after injection. They can be stable for long periods, even at room temperature, due to stabilizing additives.

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10
Q

What is the aim of recombinant vector vaccines and what are their types?

A

Recombinant vector vaccines use non-pathogenic or attenuated organisms engineered to express pathogen antigens to imitate transient infection. They can be viral or bacterial, such as Vaccinia virus,
Canarypox, or BCG strain of Mycobacterium bovis, and aim to produce a strong immune response and memory.

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11
Q

What are recombinant viral vaccines, and what are their advantages and potential drawbacks?

A

Recombinant viral vaccines use genetically engineered viruses, like adenovirus or vesicular stomatitis virus, to deliver pathogen antigens and stimulate an immune response. They are advantageous because they can closely mimic a natural infection, producing strong immunological memory, are flexible in design, and are relatively safe compared to live attenuated pathogens. However, their drawbacks include the unpredictability of individual responses to the engineered virus, the need for refrigeration during transport, the potential to cause illness in immunocompromised individuals, and the possibility that pre-existing immunity against the vector could reduce vaccine effectiveness.

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12
Q

What challenges exist in the development of the “ideal vaccine”?

A

The ideal vaccine should be safe, induce the appropriate immune response (e.g., mucosal IgA or high antibody titer), generate T and B cell memory, be stable and easy to transport, and not require repeated boosting to maintain compliance.

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13
Q

How does the SARS-CoV-2 virus use its spike protein to infect host cells?

A

SARS-CoV-2 uses a densely glycosylated spike (S) protein that binds to the ACE2 receptor on host cells. The spike protein is in a metastable pre-fusion conformation that undergoes structural rearrangement upon binding, allowing fusion of the viral and host cell membranes.

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14
Q

What is the significance of the conformational change in the S protein for vaccine development?

A

The conformational change in the S protein exposes the receptor-binding domain, which is essential for ACE2 receptor binding. Structural studies of mutations that lock the S protein in the open form can inform vaccine design to target more stable and accessible viral epitopes.

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15
Q

What are the main challenges in developing a vaccine strategy for COVID-19?

A

The challenges include inducing neutralizing antibodies to block viral entry, targeting the correct epitopes on the virus’s surface, and the potential for escape mutants that could evade the immune response induced by the vaccine.

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16
Q

Describe the RNA COVID-19 vaccines developed by Moderna and Pfizer-BioNTech.

A

Moderna’s mRNA-1273 vaccine encodes the full S protein, while Pfizer-BioNTech’s BNT162b2 also encodes the full S protein, and BNT162b1 encodes only the RBD. Both vaccines use mRNA stabilized by modified UTRs, a poly-A tail, and optimized codons, delivered via lipid nanoparticles.

17
Q

What is the Oxford vaccine strategy using ChAdOx1?

A

The Oxford vaccine, ChAdOx1, uses a chimpanzee adenovirus vector engineered to express the COVID-19 spike protein. It aims to produce a strong immune response by mimicking a natural infection and is advantageous due to its ability to replicate and its native antigen conformation.

18
Q

How is the adenovirus vector made safe for vaccine use?

A

Safety is achieved by deleting certain regions (E1, E3) of the adenovirus genome, which are necessary for replication. This creates a replication-defective virus that can still express the target antigen but cannot cause an adenovirus infection.

19
Q

How are viral particles for the adenovirus vector vaccine produced?

A

Viral particles are produced in HEK293 cells, a cell line that has been transfected with the missing viral components. The engineered virus can then replicate within these cells, allowing for the production of viral particles in high yield for vaccine use.