Lecture 20 - Vaccine Flashcards

1
Q

Which virus spread rapidly - epidemic?

A

Flu, Rota/Noro

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2
Q

Which virus cause mortality?

A

Flu, HIV

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3
Q

Which virus cause morbidity I.e. big burden of disease?

A

HPV, HIV,HCV

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4
Q

Which are the emerging viruses?

A

Pandemic flu, SARS

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5
Q

What is prophylactic vaccination?

A

Development of immunity in susceptible host

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6
Q

What is therapeutic vaccination?

A

Vaccination to augment or induce effective immunity in person previously infected

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7
Q

What is the aim of vaccination?

A

To prevent or modify disease caused by virus

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8
Q

What kind of immune response do we need to induce?

A

One that is protective and durable

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9
Q

What is vaccination protective against?

A

Different strains I.e. genetic diversity

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10
Q

What is the ultimate aim of viral vaccine?

A

Eradication I.e. small pox, Rinderpest and Polio

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11
Q

What is the order of how vaccines work?

A

Attenuated virus Inactivated virus Single recombinant protein Virus like particle DNA vaccine Recombinant virus

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12
Q

What are the non-living virus?

A

Hepatitis A/Hepatitis B virus Influenza A/ Influenza B virus Rabies virus Papilloma virus Tick-borne encephalitis Japanese encephalitis

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13
Q

What is a mixture of non living and live virus?

A

Poliovirus type 1,2,3

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14
Q

What are examples of live virus?

A

Measles, mumps, Rubella virus (MMR) Varicella/zoster Variola (vaccinia) Rotavirus.
Yellow fever virus

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15
Q

What does weakened virus do?

A

Replicate sufficiently in the host to induce a protective immune response without causing disease

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16
Q

What are examples of live attenuated virus vaccines?

A

Rotravirus (1998-1999, 2006) Varicella (1995) Measles Mumps MMR (1971) Rubella Polio-Sabin (1960) Adenovirus Yellow fever.
small pox

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17
Q

What are methods of Attenuation?

A

Repeated passage in a different host Repeated passage in cold.
Reassortment with attenuated genes

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18
Q

What are mechanisms of attenuation?

A

Receptor interaction with host cell Gene expression and replication Virion maturation

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19
Q

What are the advantages of live attenuated virus vaccine?

A
Stimulate broad immune response           Neutralising antibodies
Secretory IgA for mucosal tissue. 
Cell mediated immunity 
All antigens are expressed 
Production costs are lower
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20
Q

What are disadvantages of live attenuated Virus vaccines?

A

Potential for genetic instability Potential for contamination Infection can persist and be more severe in the immuno compromised

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21
Q

What happens with treatment with formalin or beta-propriolactone?

A

Large batches of live virus inactivated

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22
Q

What are examples of inactivated whole virus vaccine?

A

Polio-Salk (1955) Influenza.
Hepatitis A
Rabies (1980)
Japanese Encephalitis

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23
Q

What are advantages of inactivated whole virus vaccines ?

A

Little risk of infection

Multiple surface proteins present (important when protective antigens are numerous or not known)

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24
Q

What are the disadvantage of inactivated whole virus vaccine?

A

Handling large volumes of virulent virus
Risk of incomplete activation (cutter incident)
Parenteral administration (inadequate induction of resistance at portal of entry)
Virus derived in culture and inactivated may not mimic forms generated during natural infection
Poor immunity or potentials disease upon subsequent infection (RSV, measles)
Immunity often brief
Require boosting
Toxicity associated with repeated exposure to foreign proteins

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25
Q

What are subunit vaccines?

A

Highly purified subviral components needed to stimulate protective immune response (i.e. surface glycoproteins)

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26
Q

What are examples of subunit vaccines?

A
Hepatitis B (1986). 
Tick borne encephalitis
27
Q

What are advantages to Subunit Vaccines?

A

Little risk of infection
Least toxic
Viable approach when no cell culture system available

28
Q

What are disadvantages of subunit vaccine?

A
Less immunogenic/innappropriafe type 
Dominant Th-2 cell response 
IgG antibody response predominantly not complement-fixing 
No CTL response 
Multi step purification process
Costly and difficult 
Proteins may lose immunogenic epitopes
Very large quantities may be needed 
Host cell protein and DNA must be removed
29
Q

What does Hepatitis B vaccine contain?

A

HBsAg adsorbed onto aluminium hydroxide adjuvant

30
Q

Where is Hepatitis B vaccine prepared from?

A

Yeast cell using Recombinant DNA technology

31
Q

What is used for patients with renal insufficiency?

A

Fendrix

32
Q

How is Fendrix adsorbed onto aluminium phosphate?

A

Adjuvanted by monophosophoryl lipid A

33
Q

New approaches to Hepatitis B vaccine

A

Rationally-designed live-attenuated Virus
Live viral vector
Replication-defective viral vectors (VRPs)
Virus-like particles (VLPs)
DNA
Peptides
Novel Adjuvants

34
Q

Virus like particles

A

Non-replicating
Self-assembling
Ordered structure and intact conformational epitopes
Particles are highly immunogenic

35
Q

What are Human Papilloma Virus based on?

A

Hollow virus-like particle assembled from Recombinant HPV coat proteins

36
Q

What are two most common High-risk HPV?

A

Types 16 and 18

37
Q

What is the percentage that two HPV types cause cervical cancer?

A

70%

38
Q

Cervarix (GSK)

A

Protect from type 16,18 and may cross protect from other strains, may result in longer protection than Gardasil

39
Q

Gardasil (MSD)

A

Targets 6,11,16,18 which together cause about 90% of all cases of genital warts

40
Q

What is the treatment of Human Papilloma Virus Vaccine?

A

Course of three Vaccine injections

Gap of two and then four months between them

41
Q

Viral diseases without Vaccines

A
West Nile
SARS
Ebola
Hepatitis C
Avian Influenza 
HIV
Small pox 
Dengue 
RSV/PIV/Metapneumovirus
42
Q

What are the molecular basis for antiviral treatment strategies?

A

HIV
Influenza
Hepatitis C virus

43
Q

Human Immunodeficiency Virus

A
Enveloped RNA-Virus
ss + strand 
Approx 9,000 nucleotides 
2 types (HIV-1,HIV-2) with several subtypes
Cross species transmission
44
Q

What are important features of HIV?

A

Reverse transcriptase RNA —> DNA
Integrase: facilitate integration into genome
Protease: needed to cleave precursor proteins

45
Q

What does HAART stand for ?

A

Highly-active anti-Retroviral Therapy

46
Q

What is the goal for Antiretroviral therapy for HIV/AIDS?

A

Reduce viral load to undetectable/ or very low

47
Q

What are examples of inhibitors used by antiretroviral Therapy?

A
Reverse transcriptase (NRTI, NNRTI)
Protease
Integrase
Fusion inhibitor Fuzeon
Entry
48
Q

Influenza A

A
Orthomyxovirus
Envelope
Surface spikes 
Hemagglutinin protein (HA)(16 types)
Neuraminidase protein (NA) (9 types)
SS (-)RNA 
8 segmented genes
49
Q

What does Influenza A undergoes

A

Antigenic shift
Antigenic drift
With hemagglutinin and Neuraminidase proteins

50
Q

What results in pandemic?

A

Antigenic shift of the hemagglutinin proteins

51
Q

What results in epidemic?

A

Antigenic drift in the H and N proteins

52
Q

What is effective against Influenza A if given early?

A

Amantidine

53
Q

What has fewer neurological side effects than amantidine ?

A

Rimantidine

54
Q

What do Amantidine and Rimantidine inhibit?

A

M2 proteins of virus to decrease hydrogen ion influx

55
Q

What are 2 fold mechanism of these agents?

A
  1. Inhibit viral uncoating as it enters the host cell
  2. Inhibit the coating process (inhibit hemagglutinin) as daughter virion prepares to leave the host cell (through increased acidity extravirally)
56
Q

What are examples of Neuraminidase inhibitor?

A

Zanamavir
Oseltamavir
Tamiflu

57
Q

What is Neuraminidase inhibitor effective against?

A

Influenza A and B virus

Active against avian influenza

58
Q

What is Neuraminidase ?

A

Surface glycoproteins of influenza A and B

59
Q

What does Neuraminidase do?

A

Cleave terminal sialic acid residues from glyoconjugate

  • allow virion release from infected cells
  • prevent aggregation of virions
  • reduces inactivation if virus by respiratory tract mucus
60
Q

What Blocks uncoating?

A

Amantidine

Rimantidine

61
Q

What Blocks release?

A

Neuraminidase inhibitor

62
Q

What is Hepatitis C Virus?

A

Enveloped
ss + RNA genome
6 serotypes known

63
Q

What does Hepatitis C Virus encode for?

A

Structural proteins

64
Q

What are the important enzymes for replication of HCV?

A
  1. NS3/4A protease

2. NS5B RNA polymerase