Treatment and prevention viruses Flashcards
1
Q
what do viral vaccines do
A
- Prevent diseases caused by viruses
- Imitate a natural infection without causing illness
- Induce an immune response against viruses in the vaccinated people
- Help the immune system to fight off future infections
2
Q
what is the herd immunity
A
this is the idea that a number of people in the population need to be immunised in order to stop the infection spread and the infection of susceptible members of the population
3
Q
what does the percentage of people in a population who need to be immunised for herd immunity depend upon
A
- effectiveness of the vaccine
- characteristic of the disease
4
Q
what is RO
A
this is the average number of transmissions per case
5
Q
how do you work out the proportion of the population that is susceptible to the virus (epidemic threshold)
A
1/R0
6
Q
what are the numbers involving R0
A
RO <1 infection dies out
R0> 1 infection will spread in the population
7
Q
how do you work out the Proportion of population that neds to be vaccinated to eliminate the virus
A
1-1/R0
8
Q
What are the type of viral vaccines
A
- Whole inactivated virus
- Synthetic peptide – don’t usually work very well
- Live attenuated virus – goes into the cell in places such as the cytoplasm and nucleus where they are detected by the immune response
- Recombinant sub-unit viral protein
- Recombinant viral vector – different virus pathogenic viral genes
- Recombinant bacterial vector – used to carry viral genes
- DNA -carries viral genes – injects into the muscle, doesn’t replicate but produces proteins into the muscle cells
- Virus like particles
9
Q
what are examples of inactivated vaccine
A
- Poliovirus Salk, influenza, hepatitis A virus and rabies
10
Q
what does inactivated vaccine do
A
- Eliminates infectivity and this doesn’t change antigenicity
11
Q
whats the problems with inactivated vaccines
A
- Incomplete inactivation risk
- Immunity is often brief, this requires boosting
12
Q
how are inactivated vaccines unactivated
A
- Large batches of live viruses inactivated by chemicals
13
Q
what are the examples of live attenuated vaccine
A
oral polio Sabin
measles
influenza (nasal spray) VZV
14
Q
How are live attenuated vaccines made
A
made by serial passage in tissue culture
15
Q
what is the issue with live attenuated vaccine
A
- Cannot be given to immunodeficient patients
- Risks of aversion
- Virus shedding
16
Q
what are the viral like particle vaccines examples
A
HBV
HPV
17
Q
How do viral like particle vaccine work
A
- Resemble the actual structure of the virus – provoke a humoral and cellular response
18
Q
what are the advantages of viral like particle vaccines
A
- Contain no genetic material – safe
- Cost effective
19
Q
what DNA vaccine is currently int he trial phase
A
- No approved human DNA vaccines yet
- Zika DNA vaccine in clinical trials, early data shows some promise
- Inject the DNA, it gets taken up and processed by dendritic cells, the dendritic cells move to the nearest lymph nodes and they are close enough to present to CD4 and CD8 T cells
20
Q
how many antivirals are there and what are they mainly used on
A
- Only about 100 antivirals
- Most on persistent diseases such as herpesvirus, HIV
21
Q
why are there few antivirals
A
- Virus life cycle is tied to the host cell, difficult to target the virus alone
- Viruses are difficult to grow
- Most virus infections are short lived
- Compound must block virus replication completely otherwise the virus will mutate and become resistant
22
Q
what hurdles do you have to go through in order to find an effective antiviral drug
A
- Antiviral effect in cells – reject
- Acceptably low toxicity in cells
- Antiviral effect in animals
- Acceptably low toxicity in animals
- Antiviral effect in humans
- Acceptably low toxicity in humans
- Compound approved for general use
23
Q
what are the specific antivirals used in
A
- Herpesvirus
- HIV
- HCV
- Influenza
24
Q
what are the drugs used to treat herpesvirus
A
- HSV, VZV antivirals such as acyclovir
25
what kind of drug is HSV
prodrug
- HSV enzyme thymidine kinase adds a phosphate
- cellular kinases adds the 2nd and 3rd phosphate which causes the chain to terminate
26
what is the action of acyclovir (HSV, VZV)
- they are chain terminators, this stops them from making the viral DNA
- Mimicks one of the 4 bases that is needed for DNA, mimicks guanosine
- Need hydroxyl group in guanosine which is missing in acyclovir
mechanism of action
- HSV enzyme thymidine kinase adds a phosphate
- cellular kinases adds the 2nd and 3rd phosphate which causes the chain to terminate
- Supportive treatment alone may be sufficient for; single episode of orogenital HSV, - uncomplicated chickenpox and shingles
27
what do antiviral drugs do (HSV VZV)
Antiviral drugs may reduce symptoms, duration of illness, viral shedding and may reduce complications
- always treat immunocompromised patients
28
describe the structure of the influenza virus
- Envelope
- Surface spikes – hemagglutinin protein HA (16types)
- Neuraminidase protein (NA) 9 TYPES
- SS RNA
- 8 segmented genes
29
what are the two antivirals used to treat viruses
- prevents it from uncoating - Amatadine
| - prevents it from being released - neuraminidase inhibitor
30
How do antivirals prevent the virus from uncoating in influenza
Amantadine
- Interacts with the influenzas M2 protein ion channel
- Blocks entry of protons into virion preventing it uncoating and placing the substances from going into the cell
- Resistance to amantadine emerges rapidly
31
How do antivirals prevent the virus from being released in influenza
Neuramindase inhibitor
- Inhibitor binds to the neuraminidase
- Blocks it action
- Prevents the virus from being released from the cell therefore it cannot infect another cell,
Amatadine prevents uncoating, neurmindase inhibitors block release
32
How are drugs used to inhibit HIV
- Block attachment and etnry inhibitor
- Fusion inhibitors
- Reverse transcriptase inhibitors – prevent RNA from being turned into DNA
- Integrase inhibitors
- Protease inhibitors – prevents maturation
33
what is the combination therapy for HIV/AIDS
HAART - highly active anti-retroviral therapy
34
what is PrEP
– people who has a partner who is HIV positive
- Daily double therapy for those at high risk for HIV infection
- Reduces risk of sexual transmission of HIV-1 by >90%
- Reduces risk of transmission by IVDU by >70%
- No resistance in trials but might be different in real world
35
How does HAART work?
- Use HIV inhibitors from different classes to maximise outcome
- Reduces viral load to undetectable/or very low
What inhibitors are used
- Block attachment and entry inhibitor
- Fusion inhibitors
- Reverse transcriptase inhibitors – prevent RNA from being turned into DNA
- Integrase inhibitors
- Protease inhibitors
36
describe the structure of hepatitis C
- made up of structural proteins and non structural proteins
37
previously what was the only drug to treat hepatitis C
interferon ribaviron – cant give people this all the time to treat drug viruses
38
what is DAAS (direct acting antivirals) (Hepatsis C)
1. A large polyprotein cleaved by NS3 on the membraneous web
2. NS5B RNA -dependent polymerase makes negative strand RNA a template for postivie stranded RNA (nucleoside and nucleotide inhibitors)
3. NS5A inhibitors block replication complex, formation and assembly
39
give the example of how to work out RO
R0 is the number of new cases that an existing case generates on average over the infectious period in a susceptible or non vaccinated population
New/existing cases = R0
R0 <1, then it will die out (eg if you have 2 existing infections and then only 1 new then 1⁄2 = 0.5)
R0=1, then it is stable (eg you have 2 existing infections and 2 new infections then 2/2 =1)
R0 >1, then it will spread (eg if you have 2 existing infections and then you get 8 new, then 8/2 =4) To eradicate an infection you need to reach R0 <1, preferably 0.
To stop the spread you need to reach R0=1
Measles has an R0=18; but we have a vaccine MMR (Measles, Mumps,
Rubella)
We want our goal R0=1,
but our existing R0 is 18, so we can stop the spread even if 1/18 still contacts measles.
But 17 people will need to be protected.
So this is represented by 1-Goal R0/Current R0
So what proportion of the population needs to be vaccinated? 1-1/18= 1-0.06 thus 94%
40
What kind of virus is the influenza virus
orthomyxovirus
41
what is the goal of HAART
```
➢ Reverse Transcriptase Inhibitors (NRTI, NNRTI)
➢ Protease Inhibitors
➢ Integrase Inhibitors
➢ Fusion Inhibitor
➢ Entry Inhibitors
```
42
what does sofosbuvir do the hepatitis C virus
Sofosbuvir stops synthesis of the growing viral RNA Chain (nucleotide analogue)
Non-nucleoside inhibitors cause allosteric changes in the NS5B itself
43
antivirals do...
not prevent infection
