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
What are subunit vaccines?
Highly purified subviral components needed to stimulate protective immune response (i.e. surface glycoproteins)
26
What are examples of subunit vaccines?
``` Hepatitis B (1986). Tick borne encephalitis ```
27
What are advantages to Subunit Vaccines?
Little risk of infection Least toxic Viable approach when no cell culture system available
28
What are disadvantages of subunit vaccine?
``` 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
What does Hepatitis B vaccine contain?
HBsAg adsorbed onto aluminium hydroxide adjuvant
30
Where is Hepatitis B vaccine prepared from?
Yeast cell using Recombinant DNA technology
31
What is used for patients with renal insufficiency?
Fendrix
32
How is Fendrix adsorbed onto aluminium phosphate?
Adjuvanted by monophosophoryl lipid A
33
New approaches to Hepatitis B vaccine
Rationally-designed live-attenuated Virus Live viral vector Replication-defective viral vectors (VRPs) Virus-like particles (VLPs) DNA Peptides Novel Adjuvants
34
Virus like particles
Non-replicating Self-assembling Ordered structure and intact conformational epitopes Particles are highly immunogenic
35
What are Human Papilloma Virus based on?
Hollow virus-like particle assembled from Recombinant HPV coat proteins
36
What are two most common High-risk HPV?
Types 16 and 18
37
What is the percentage that two HPV types cause cervical cancer?
70%
38
Cervarix (GSK)
Protect from type 16,18 and may cross protect from other strains, may result in longer protection than Gardasil
39
Gardasil (MSD)
Targets 6,11,16,18 which together cause about 90% of all cases of genital warts
40
What is the treatment of Human Papilloma Virus Vaccine?
Course of three Vaccine injections | Gap of two and then four months between them
41
Viral diseases without Vaccines
``` West Nile SARS Ebola Hepatitis C Avian Influenza HIV Small pox Dengue RSV/PIV/Metapneumovirus ```
42
What are the molecular basis for antiviral treatment strategies?
HIV Influenza Hepatitis C virus
43
Human Immunodeficiency Virus
``` Enveloped RNA-Virus ss + strand Approx 9,000 nucleotides 2 types (HIV-1,HIV-2) with several subtypes Cross species transmission ```
44
What are important features of HIV?
Reverse transcriptase RNA —> DNA Integrase: facilitate integration into genome Protease: needed to cleave precursor proteins
45
What does HAART stand for ?
Highly-active anti-Retroviral Therapy
46
What is the goal for Antiretroviral therapy for HIV/AIDS?
Reduce viral load to undetectable/ or very low
47
What are examples of inhibitors used by antiretroviral Therapy?
``` Reverse transcriptase (NRTI, NNRTI) Protease Integrase Fusion inhibitor Fuzeon Entry ```
48
Influenza A
``` Orthomyxovirus Envelope Surface spikes Hemagglutinin protein (HA)(16 types) Neuraminidase protein (NA) (9 types) SS (-)RNA 8 segmented genes ```
49
What does Influenza A undergoes
Antigenic shift Antigenic drift With hemagglutinin and Neuraminidase proteins
50
What results in pandemic?
Antigenic shift of the hemagglutinin proteins
51
What results in epidemic?
Antigenic drift in the H and N proteins
52
What is effective against Influenza A if given early?
Amantidine
53
What has fewer neurological side effects than amantidine ?
Rimantidine
54
What do Amantidine and Rimantidine inhibit?
M2 proteins of virus to decrease hydrogen ion influx
55
What are 2 fold mechanism of these agents?
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
What are examples of Neuraminidase inhibitor?
Zanamavir Oseltamavir Tamiflu
57
What is Neuraminidase inhibitor effective against?
Influenza A and B virus | Active against avian influenza
58
What is Neuraminidase ?
Surface glycoproteins of influenza A and B
59
What does Neuraminidase do?
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
What Blocks uncoating?
Amantidine | Rimantidine
61
What Blocks release?
Neuraminidase inhibitor
62
What is Hepatitis C Virus?
Enveloped ss + RNA genome 6 serotypes known
63
What does Hepatitis C Virus encode for?
Structural proteins
64
What are the important enzymes for replication of HCV?
1. NS3/4A protease | 2. NS5B RNA polymerase