Viral vaccines II Flashcards
1
Q
What are the different types of RNA vaccines? (2)
A
- Non-replicating mRNA
- Virally-derived self-amplifying mRNA (SAM)
2
Q
What are the characteristics of using non-replicating mRNA techniques in the development of RNA vaccines? (3)
A
- Gene of interest
- Flanking untranslated regions
- 5’ cap and polyA tail
3
Q
Virally-derived self-amplifying mRNA is mostly based on which type of genomes?
A
Alphavirus genomes
4
Q
True or false: RNA vaccines produce a small amount of antigen from an extremely small dose of vaccine
A
False -> Large amount of antigen production from an extremely small dose of vaccine
5
Q
How is transient expression of encoded proteins ensured using RNA vaccines?
A
Delivery into cytosol via lipid nanoparticles
6
Q
What are the advantages of RNA vaccines? (3)
A
- Safe
- Good induction of cellular- and humoral immune response
- Scalable
7
Q
What are the disadvantages of RNA vaccines? (2)
A
- Stability
- SAM: size constraints/dsRNA formation
8
Q
What is the main idea of dendritic cell (DC) vaccines?
A
Training immune system of your patients (ex vivo)
9
Q
What are the steps of the experimental stage of DC vaccines? (6)
A
- Isolation of PBMCs
- Selection of monocytes
- Culture immature DCs
- Maturation -> mature DCs
- Training
- Putting back in patients
10
Q
What are the advantages of DC vaccines? (3)
A
- Good induction of cellular immune response
- Induction of CTLs
- Individual/tailor-made vaccines
11
Q
What are the disadvantages of DC vaccines? (3)
A
- Individual/tailor-made vaccines
- Labor-intensive
- Expensive
12
Q
What is a viral vector?
A
Tool used by molecular biologist to deliver genetic material into cells/host
13
Q
What are viral vector-based vaccines?
A
Use of vectors to carry selected genes from another pathogen for immunization purposes
14
Q
What are the advantages of vector-based vaccines? (4)
A
- Safe
- Intrinsic adjuvant
- Induction of natural immunity
- Marker vaccine
15
Q
What are the disadvantages of vector-based vaccines? (3)
A
- Multiple dosages required
- Pre-existing immunity
- Adaptive immune responses to vector
16
Q
Difference with ???.
A
Viral-vector overexpressing of any protein
17
Q
What parameters do you need to think about when making a viral-vector vaccine? (7)
A
- Vector
- Antigen
- Design antigen
- Only include genes from the pathogen?
- Dose
- Amount of dosages
- Administration route
18
Q
Which viruses are the best studied vectors? (2)
A
- Adenovirus
- Poxvirus
19
Q
Which parameters do you need to take into account when choosing a vector? (3)
A
- Replication-competent/deficient
- Pre-existing immunity
- Types of immunity induced
20
Q
What kind of immune response is induced by adenovirus? (3)
A
- Strong CD8+ T cell effector memory response
- Weak CD8+ central memory response
- Strong humoral immunity
21
Q
What is the main challenge with adenoviruses in viral vector-based vaccines?
A
Pre-existing immunity
22
Q
What kind of immune response is induced by poxvirus?
A
More of a mixture of effector and central memory CD8+ T cells
23
Q
How can you ensure stability of your antigen?
A
Inducing mutations
24
Q
What are the options when designing an antigen for viral vector-based vaccines? (3)
A
- Full-length
- Peptides
- Modified antigens
25
What are the types of COVID-19 vaccine platforms? (4)
1. Inactivated virus
2. mRNA
3. Viral vector
4. Protein subunit
26
Which parameters do you need to take into account when determining which vaccine to use in your population? (5)
1. Price
2. Logistics
3. Safety
4. Efficacy
5. Immunogenicity
27
What are the difficulties in using an mRNA vaccine in Africa? (3)
1. Cost
2. Cold chain
3. Politics
28
What is meant with vaccine effectiveness?
The ability of a vaccine to protect an individual or population from an infectious disease
29
What is meant with vaccine protection?
Relative term that depends on the situation
30
Which parameters are important to consider when determining vaccine protection? (3)
1. What does it protect against?
2. Type of pathogen and population
3. Difference between vaccine formulations
31
Vaccine protection: what types of protection (against what) can you choose from? (4)
1. Infection
2. Disease
3. Transmission
4. Hospitalization
32
How can vaccine efficacy be adjusted?
Boosting
33
Which factors can influence vaccine efficacy? (4)
1. Vaccine platform
2. Boosting
3. Dose
4. Host-and viral factors
34
Which host-and viral factors can influence vaccine efficacy? (4)
1. Immune factors
2. Viral variant factors
3. Demographic factors
4. Vaccine access factors
35
What is meant with the immunogenicity of a vaccine?
Ability of a vaccine to stimulate an immune response to the vaccine product
36
Why are immunogenicity studies important? (3)
1. Easy high-throughput read-out -> diagnostic value
2. Improving vaccine formulation
3. Adapting vaccination policy
37
What is meant with the correlate of protection?
The immune response a vaccine or natural infection needs to induce in order to achieve immunological memory
38
Why is the correlate of protection important? (4)
1. Diagnostic value of the clinic
2. Measure for vaccine efficacy
3. Difficult to study in humans
4. Immune profiles of protection
39
What are the different immune components used for assessing immunogenicity? (4)
1. Neutralizing antibodies
2. Non-neutralizing antibodies
3. CD4+ T cells
4. CD8+ T cells
40
Which functions do antibodies have besides their neutralizing ability?
Fc-mediated antibody functions
41
What is an example of differences between vaccines?
Some vaccine formulations are better T cell inducers
42
Why is it beneficial for the virus to adapt to its environment? (3)
1. Increased transmission
2. Immune evasion
3. Reduce vaccine efficacy
43
True or false: T cells decline faster post infection than antibodies
False
44
What are important vaccine access factors to consider? (4)
1. Timing
2. Location
3. Booster effect
4. Vaccine inequality
45
What are important hosts-and demographic factors to consider affecting vaccine efficacy? (4)
1. Infection history affects immunogenicity
2. Age
3. immunocompromised
4. Vaccine hesitancy
46
Can you modify immunogenicity of your vaccine by combining different vaccines?
Yes
47
Why are mRNA-based vaccine platforms able to quickly adapt to new variants?
They are bivalent vaccines
48
Which factors play a role in vaccine hesitancy? (4)
1. Religion and mistrust
2. Fear of the unknown
3. Side-effects
4. (Lack of) communication
49
What are vaccine-preventable diseases with the greatest global health burden? (7)
1. Rabies
2. Yellow fever
3. Ebola
4. HAV
5. HBV
6. Typhoid fever
7. Dengue
50
What are the main challenges in achieving high vaccination coverage in tropical regions? (7)
1. Financial
2. Economic
3. Logistical
4. Attitude
5. Political
6. Health
7. Vaccine safety
51
Which infectious disease is easy to acquire but successfully combatted by improving hygiene in The Netherlands?
Hepatitis A
52
True or false: mass vaccination for HAV is implemented for most countries
False -> not implemented in most countries, travellers vaccinated only
53
True or false: the burden of vaccine-preventable disease is higher in high-income settings
False -> higher in low-income settings
54
What are the transmission routes of smallpox? (2)
1. Direct contact
2. Aerosols
55
Name examples where smallpox and warfare were connected in the past (2)
1. The Spanish introduced smallpox to the Aztec and Incas
2. British forces used smallpox blankets -> biological warfare
56
What does variolation mean?
Intentional experimental infection with virus
57
In the 15th century, what was the case-fatality rate of the variolation procedure?
~2%
58
Besides variolation, experimental inoculations were performed for other viruses. Which viruses? (2)
1. Rinderpest
2. Measles
59
What were Edward Jenner's main observations? (2)
1. Milkmaids rarely had pox lesions
2. Brood parasitism of the cuckoo
60
What was Edward Jenner's main hypothesis?
Protection afforded by cowpox
61
Which vaccine transmission routes were used in the past? (3)
1. Arm-to-arm -> mid 19th century
2. Production in cattle -> 1805
3. Freeze-dried -> 1940
62
What are the conditions to make a disease eradicable? (5)
1. Limited pathogen variability
2. No animal reservoir
3. No persistent infections
4. Effective vaccine available
5. Good diagnostics methods
63
In what year was the smallpox eradication program started?
1967
64
Vaccination can induce protection against? (4)
1. Infection
2. Transmission
3. Disease
4. Death
65
In the past, which complications could occur after vaccinia vaccination? (7)
1. Progressive vaccinia
2. Generalized vaccinia
3. Contact vaccinia
4. Secondary infections
5. Postvaccine encephalitis
6. Eczema vaccinatum
7. Fetal vaccinia
66
In which subset of patients did progressive vaccinia mostly occur as vaccinia vaccination side effect?
Immunocompromised patients
67
Is cowpox a cow virus?
No -> rodent virus
68
How did the chicken cholera vaccine came to be? (2)
Bacteria forgotten during hot summer holidays -> heat treatment/attenuation of bacteria
69
What was the function of the chamberland filter?
Removes bacteria from solution
70
History of vaccines: attenuation was applied to which viruses? (4)
1. Anthrax
2. Rabies
3. TB
4. Diphteria
71
When was poliomyelitis first described?
1789
72
How many serotypes does poliovirus have?
3
73
Where does poliovirus replicate in the body? (3)
1. Pharynx
2. GI tract
3. Local lymphatics
74
Hematological spread of poliovirus goes to? (2)
1. Lymphatics
2. CNS
75
How does destruction of motor neurons occur due to poliovirus infection?
Viral spread along nerve fibers
76
What is the most likely outcome of poliovirus infection?
~90% of infections are asymptomatic
77
When was the last endemic case of poliovirus infection?
1980
78
How many poliovirus strains are eradicated nowadays?
2 out of 3
79
Which two drops in number of poliocases were observed?
First drop: inactivated vaccine
Second drop: live oral vaccine
80
How was the live-attenuated measles virus vaccine attenuated? Which difficulty arose?
Propagation in many different cell lines -> difficult to determine passage history
81
Why were there still some measles outbreaks after the vaccine was licensed?
Lack of second dose
82
When was rinderpest eradicated?
2011
83
What are the main goals of changing the age of the second dose of measles vaccination from 9 years old to 3 years old? (2)
1. Less scary for the child
2. Better protection
84
