Viral vaccines I Flashcards by Anouk T

What is passive immunization?

Administration of antibodies to an unimmunized person from an immune subject to provide temporary protection against a microbial agent or toxin

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What kind of protection is provided by passive immunization?

Protection provided by antibodies created outside the body

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What is a well known example of passive immunization?

Diphtheria antitoxin (DAT)

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How is active immunity defined?

Immunity to a pathogen that occurs following exposure to this pathogen

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What are the functions of antibodies? (3)

Neutralization
Fc-receptor interaction -> ADCP and ADCC
Complement activation

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What are the two forms of passive immunization?

Natural
Artifical

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What is an example of natural passive immunization?

Maternal IgG transportation by the neonatal Fc receptor across the placenta

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How can we improve passive immunization in newborns before conception, during pregnancy and postnatal?

Before conception: MMR vaccine
During pregnancy: booster vaccines
Postnatal: breastfeeding

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What are examples of booster vaccines provided to the mother to improve passive immunization in newborns? (2)

Pertussis
RSV

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What is the best moment in pregnancy to administer a pertussis booster vaccine to the mother?

~22 weeks

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What kind of vaccines are generally avoided during pregnancy because of a theoretical risk to the fetus?

Live vaccines

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Which vaccines are associated with an adverse pregnancy outcome? How do you prevent this?

MMR vaccines –> vaccinate BEFORE conception

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What can be side effects of passive immunization? (3)

Allergic response
Serum sickness to proteins from non-human source
Local response

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What are examples of artificial passive immunization? (2)

Monoclonal antibodies
Polyclonal antibodies

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What are the characteristic features of monoclonal antibodies as means for passive immunization? (4)

Cheap
Mixed ab
Bind different areas of specific molecule
Tolerant of small changes in protein structures

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What are the characteristic features of polyclonal antibodies as means for passive immunization? (4)

Expensive
Single Ab species
Only bind single specific site
May recognize a particular protein form

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What are the indications to chose passive immunization? (2)

Insufficient antibody synthesis
Exposure to disease in case of absence of existing immunity and that disease is likely to cause disease

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Which types of antibody deficiencies exist? (2)

Inherited (primary) antibody deficiencies
Acquired (secondary) antibody deficiencies

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Name an example of an inherited antibody deficiency

XLA: X-linked agammaglobulinemia

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What are examples of how people acquire secondary antibody deficiencies? (2)

Chemotherapy
Immunosuppressive medication

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Name examples of viruses known to cause complications indicating the need for passive immunization? (2)

RSV
Rabies

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If someone is already vaccinated against rabies virus, what do you administer? How often?

Post-exposure vaccination (2x)

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If someone has not been vaccinated against rabies virus, what do you administer?

Vaccination 4x + HRIG (human-anti rabies immunoglobulins)

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What is the main challenge in treating non-vaccinated rabies patients in underdeveloped countries?

Immunoglobulins are not available –> you have to administer it very soon after

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What is meant with the vaccination paradox?

The ones you want to vaccinate most, are the hardest to protect

What are the natural defenses against viruses? (3)

1. Barriers 2. Cells 3. Molecules

What are the characteristics of the natural defenses? (3)

1. Fast 2. Aspecific 3. No memory formation

Which cell types are involved in the innate natural defense? (3)

1. Granulocytes 2. Macrophages 3. NK cells

Which molecules are involved in the innate natural defense? (3)

1. Interferon 2. Complement 3. Lysozymes

Which two categories of vaccine formulation exist?

1. Classical 2. Novel

What are examples of classical vaccine formulations? (3)

1. Live-attenuated vaccines 2. Inactivated vaccines 3. Subunit vaccines

What are examples of novel vaccine formulations? (5)

1. DNA vaccines 2. Vector-based vaccines 3. Virus-like particles 4. Antigen-loading autologous cells (DC) 5. RNA vaccines

Which technique is required for the development of novel vaccine formulations?

Recombinant DNA technology

What are examples of viruses that are used for live-attenuated vaccines? (6)

1. MMR 2. VZV 3. Yellow fever 4. Influenza 5. TB 6. BCG

What are the two groups of live-attenuated vaccines?

1. Virus that does not normally infect humans, but closely related to human virus 2. Take human pathogen and attenuate it -> then give it back

What is an example of a human pathogen that has been attenuated before giving it back to humans? How was this achieved?

Mumps -> cultured in embryonic chicken eggs and cells

What is an example of a virus that does not normally infect humans/cause disease, but does protect humans against a human variant of this virus?

Cowpox to protect against smallpox

What are the advantages of live-attenuated vaccines (2)

1. Immune response resembles natural immunity 2. Long-lasting protection after single dose

Live-attuenated vaccines: What is the benefit of in host replication of the pathogen?

Immune response resembles natural immunity (induction of CD4, CD8 and antibodies)

What are the disadvantages of live-attuenated vaccines (3)

1. Safety risk in immunocompromised 2. Possibility to revert to wildtype 3. Interference by maternal antibodies

What is the main benefit of an inactivated vaccine?

Eliminating infectivity without compromising immunogenicity

Name some examples of viruses where inactivated vaccines are used (4)

1. Influenza 2. Polio 3. HAV 4. Bordetella pertussis

How can you inactivate a virus to generate an inactivated vaccine? (3)

1. Chemicals (formalin) 2. Heat 3. Radiation

What is a crucial requirement to induce an effective immune response using an inactivated vaccine?

Addition of adjuvant

What is the main advantage of inactivated vaccines?

Safety

What are the disadvantages of inactivated vaccines? (4)

1. Multiple dosages required 2. Short-lasting immunity 3. Poor CD8+ T cell response 4. Risk of priming for enhanced disease in certain viruses

Inactivated vaccines may increase the risk of priming for enhanced disease. For which viruses is this the case? (2)

1. Paramyxoviruses 2. Feline coronavirus

What are the two manufacturing options for subunit vaccines?

1. Non-recombinant 2. Recombinant

What does non-recombinant manufacturing of subunit vaccines entail?

Fractionation of pathogen -> purify proteins

What does recombinant manufacturing of subunit vaccines entail?

Express gene of interest in bacteria/yeast/cells -> purify proteins

What are the most common antigens in subunit vaccines?

Capsid- or membrane proteins

True or false: adjuvants are often required for induction of effective immune responses when using subunit vaccines

True

What are the advantages of subunit vaccines? (3)

1. Safe 2. Selection of subunit -> targeted immune response 3. Marker vaccine possible

What is the purpose of a marker vaccine?

In live stock: differentiating infected from vaccinated animals

How can you use a subunit vaccine as a marker vaccine?

Discriminate animals that have been infected with a wildtype virus as opposed to animals that have been vaccinated

How do you determine if live-stock is infected with a wild-type virus or the vaccine?

Screen entire herds with serology assay

Why are the use of marker vaccines important for the live-stock sector?

If livestock becomes ill, you want to know if you have to kill your animals

What are the disadvantages of a subunit vaccine? (3)

1. Poorly immunogenic -> multiple dosages 2. Short-lastig immunity 3. Poor induction of CD8 T cell response

Why are subunit vaccines unable to induce a proper CD8+ T cell response?

No proteins endogenously produced

Why are viral-like particle vaccines more potent?

Density of protein on the surface -> resembles wild type pathogen

Name examples of VLP viruses (3)

1. HBV 2. HPV 3. HEV

What are the advantages of VLP vaccines? (4)

1. Safe 2. Structural similarity with viruses 3. Selection of subunit -> targeted immune response 4. Marker vaccine possible

What are the disadvantages of VLP vaccines? (4)

1. Poorly immunogenic -> multiple dosages 2. Short-lastig immunity 3. Poor induction of CD8 T cell response 4. Preexisting immunity to VLP vector

What is an adjuvant?

Pharmacological/immunological agent that enhances the immune response to a vaccine

What are the mechanisms by which an adjuvant can work? (4)

1. Antigen stabilization/delayed release 2. Enhanced uptake antigen macrophages 3. Activation co-stimulatory molecules 4. Improve delivery of antigens -> cytosol

How is the effect of antigen stabilization/delayed release caused by adding adjuvants also called?

Depot effect

How does activation of co-stimulatory molecules influence immunity? (2)

1. Influence innate immunity 2. Skew CD4 to Th2 response -> antibody production

Name examples of adjuvants in virology (6)

1. Aluminium salts 2. Mineral oils 3. Bacterial products 4. Detergents 5. ISCOMs 6. Cytokines

What is the working mechanism of DNA vaccines?

Genes that encode antigens of interest as bacterial plasmid DNA

How is protein formation ensured by DNA vaccines? (3)

1. DNA taken up by host cells 2. Transient expression of encoded genes 3. Protein formation

True or false: Immunogenicity of DNA vaccines is limited in humans, but works well in small laboratory animals

True

What is the main challenge with DNA vaccines?

Administration

Originally the 'gene gun' was used for administration of DNA vaccines. How does it work? (3)

1. Gold particles coated with DNA 2. Taken up by macrophages 3. Presentation to B- and T cells

Which administration method is currently used for DNA vaccines?

Gas injections

What are the advantages of DNA vaccines? (5)

1. Easy to produce 2. Induction humoral immune responses 3. Induction CD4/CD8 4. Very stable 5. Can encompass large inserts

What are the disadvantages of DNA vaccines? (2)

1. Poorly protective 2. Perceived risk of genome integration