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miguel > Viral Vaccines > Flashcards

Viral Vaccines Flashcards

1
Q

WHO states the 2 most significant developments which have improved the health of children are:

A

Clean water
Vaccination

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2
Q

Variolation

A

Ancient method
Recovered patients had life-long immunity
Material from infected individuals given to healthy people may result in milder disease and subsequent protection
10 fold reduction in disease incidence
2-3% died
Eg smallpox virus

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3
Q

Smallpox vaccine

A

Edward Jenner
Dairy maids infected with cowpox (mild disease) - resistant to smallpox
1796 - inoculated 8 year old boy with fluid from dairy maid cowpox posture; 6 weeks later exposed to smallpox => no symptoms

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4
Q

Why was global eradication possible for Smallpox?

A

Virus biology
- no animal reservoir
- lifelong immunity
- no overt symptoms
- one serotype
- good vaccine (vaccinia virus)

Global commitment
- Governments
- WHO (1965)

1979 - 1/2 viruses eradicated ever

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5
Q

In what year was MMR vaccine introduced in the UK?

A

1988

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6
Q

3 examples of live attenuated vaccines

A

MMR
Polio
Influenza
Smallpox

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7
Q

3 examples of inactivated/whole vaccines

A

Hep A
Rabies
Japanese encephalitis
(Influenza)

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8
Q

Distribution of vaccines requires strict ______________ control of vaccine stock.

A

Temperature

(Difficult in hot climates in resource poor countries)

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9
Q

Whole inactivated vaccines

A

Virus grown in cell culture or eggs
Extract
Chemical inactivation e.g. formaldehyde

No possibility of infection - control
Duration of protective immunity generally less than live attenuated vaccines

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10
Q

Inactivated vaccines - split

A

Virus grown in cell culture or eggs
Lyse culture
Extract virus vaccine antigen eg F surface protein in Influenza
Purify vaccine antigen

No possibility of infection
Duration if immunity less than for live attenuated vaccines
E.g.influenza HA = vaccine target of interest

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11
Q

Subunit vaccines

A

Recombinant subunit vaccines

Identify potential vaccine antigens
Obtain cDNA copies of genes
Antigen gene cloned into expression vector
Antigen expression in suitable cells (eukaryotic, bacteria, yeast)
Antigen purification
Vaccine formation - add adjuvants
-> modulates immune response

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12
Q

Adjuvants

A

Greatly enhances immune response to antigens
e.g. aluminium hydroxide

ISCOMs (immune stimulating complexes); oil/water emulsions and toll-like receptor agonist = undergoing research

Influenza no adjuvants in adults
Influenza adjuvants needed in elderly

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13
Q

_______ __________ ______________ leads to herd immunity.

A

High vaccine uptake - 90%

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14
Q

How do vaccines modulate the acquired immune system?

A

Vaccine antigen introduced to body (Mucosal or Parenteral) -> Viral antigen taken up by APCs -> present antigen to B and T cells in correct conformation in LNs -> Clonal expansion of epiptope-specific memory B and T cells ->
Accelerated response to virus upon infection -> protection from disease due to Tc cells and neutralising Abs

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15
Q

Most common vaccine adverse events

A

Injection site hypersensitivity
Injection site oedema
Rash
Myalgia
Fever
Headache

VAERS US, 1990-2001

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16
Q

What does VAERS stand for?

A

Vaccine Adverse Events Reporting System

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17
Q

Eczema vaccinatum

A

Smallpox vaccine adverse events
Frequency => 10-42 cases/million vaccinees

18
Q

Vaccines versus therapeutics

A

Healthy individuals
Mass administration
Disease prevention
Low risk tolerance
Low cost

19
Q

Vaccines versus therapeutics

A

Sick individuals
Targeted administration
Disease treatment
High risk tolerance
High cost

20
Q

Obstacles to vaccination in infancy

A

Immune system not fully mature
Maternal antibody restricts live vaccines
False contraindications
Parental fears
Adverse publicity

21
Q

Vaccine contra-indications

A

Acute illness
Definite severe or generalised reaction to preceding dose
Avoid live vaccines in pregnancy
Care with live vaccines in immunocompromised patients

22
Q

Do multiple vaccines overwhelm immune system?

A

Childs immune system can cope with 11000 immunological challenges at once
<0.1% of the immune system is used after MMR

23
Q

Does the MMR vaccine cause autism?

A

Population based study in Denmark 1991-1998
N = 537,303 kids
MMR vaccine = 440,655
316 autistic children
442 autistic spectrum
No increased risk with vaccine

MMR vs autism in Japan
Stopped giving MMR vaccine
No change in incidence of autism

24
Q

Synthetic peptide vaccines

A

Synthesis of chemically defined antigens

Require:
- antigen purification
- carrier protein conjugation - provide helper T-cell epitopes (essential for B-cell activation, memory and Ab production e.g. tetanus toxoid)

25
Q

Recombinant subunit vaccines are:

A

Novel expression systems or
Novel formulations

26
Q

Recombinant viral vaccines typically involve: (2)

A

Reverse genetics (influenza, RSV)
Multi-valent antigen expression vectors

27
Q

Major challenges for viral vaccines

A

Viral quasi-species and antigenic variability
- influenza

Overcoming poor immunogenicity of WT viral antigens
- RSV

Formulations
- induction of sufficiently strong, long lasting, and safe immune responses

Live attenuated vs subunit

Mucosal vs parenteral

28
Q

Viral quasi-species

A

Population structure of viruses with a large number of variant genomes.
Result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds

29
Q

Example of inactivated/split vaccine

A

Influenza

30
Q

3 Examples of subunit vaccines

A

Hep B
HPV
SARS - CoV- 2

31
Q

Virus attenuation and considerations

A

Repeated passage in non-natural cells -> reduced ability to replicate in natural host - cell culture adaption.
Induce sub-clinical infection AND induce protective immune responses - Usually long lasting

Complicating risk
- Reconversion to wild-type
- Contaminating infectious agents in cell culture
- Cold chain

32
Q

Herd immunity

A

Sufficient number of vaccinated people to protect those unvaccinated eg immunocompromised (can’t cope with live unattenuated virus) or those with allergies (eg egg proteins)

33
Q

All medical interventions carry risks of adverse events so should calculate:

A

Vaccine risk/benefit ratio

Low disease morbidity and mortality = low risk acceptable
High disease morbidity and mortality = higher risk acceptable

34
Q

Serious adverse events of vaccines

A

Life threatening illness
Death

35
Q

Future Vaccines

A

Synthetic peptides
Recombinant subunit vaccines
Recombinant viral vaccines

36
Q

Carrier proteins

A

Conjugated to peptide antigens which provide helper T cell epitopes - Essential for B cell activation, memory and Ab production

Eg Tetanus toxoid and Diptheria toxoid

37
Q

Polio

A

Generally benign
1% flaccid paralysis
Vast amount of people infected
Dime for polio research
Live tenanted vaccine no longer used in favour of inactivated vaccine

38
Q

Polio London patient

A

Individual travelled to London
Had been given live attenuated vaccine,no longer used in England
Virus was shedded and found in sewerage

Live attenuated vaccine no longer used as there is a small possibility of virus returning to WT
->excreted into waste-water
-> infectious

39
Q

What do you want in a vaccine?

A

Sub-clinical infection with no symptoms
Stimulate the immune response without pathology

40
Q

Groups who should not be given live attenuated vaccine

A

HIV patient
Cancer patient
Allergies
->allergy to egg protein

41
Q

Efficacy of MMR vaccine

A

90-92%
=> herd immunity

miguel (8 decks)

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