Prevention and treatment of viral disease

Question 1

Prophylaxis

Answer 1

preventing disease before aetiologic agent is acquired, by vaccination or giving drug before infection.

Question 2

Therapy

Answer 2

treating disease after host has been infected

Question 3

Vaccines

Answer 3

Prophylactic
Live or inactive
Herd immunity or defined target group 
Safety > efficacy (RSV vaccine in 1970s)
Controlled by Governments and WHO

Question 4

Antiviral drugs

Answer 4

Therapeutic
Random screen or rational design
Define target group: very sick or over the counter
Prescribed on an individual basis

Question 5

Immunological basis of protection after vaccination

Answer 5

1st Infection: Acquired specific immune response

2nd Exposure: Response is rapid and potent, only mild/ inapparent infection

Question 6

What led to the eradication of smallpox?

Answer 6

Scrape pox virus spore onto arm to give mild infection that would protect them against worse
No animal reservoir for smallpox (only human)
No latent or persistent infection (acute)
Smallpox was an easily recognised disease

Question 7

Smallpox vaccine

Answer 7

effective against all strains of virus

Potent, low cost, abundance, heat stabile, easily administered

Question 8

Live attenuated vaccine

Answer 8

live virus has its virulence reduced and then is administered to the patient

Question 9

Inactivated vaccine

Answer 9

virus genome is destroyed so that it is still stimulates a response but can no longer be infectious
given with adjuvant

Question 10

Purified subunit vaccine

Answer 10

viral genome treated with proteases which chop it into subunits
these have antigens that can trigger an immune response.

Question 11

Cloning vaccine

Answer 11

viral genome cloned in a bacterium and the copies of the genome are either:
Injected into people
Put into virus-like particles

Question 12

Give 7 examples of viruses for which live attenuated vaccines are effective against

Answer 12

Influenza
Measles 
Mumps
Rubella
Polio
Varicella zoster virus
Smallpox

Question 13

Give 3 examples of viruses for which inactivated vaccines are effective against

Answer 13

Hepatitis A
Polio
Rabies

Question 14

Give an example of a virus for which purified subunit vaccines are effective against

Answer 14

Influenza

Question 15

Give 2 examples of viruses for which cloned subunit vaccines are effective against

Answer 15

Hepatitis B

Human papillomavirus

Question 16

How are Live Attenuated Vaccines made?

Answer 16

Pathogenic virus isolated from patient and grown in human cultured cells
Cultured virus used to infect monkey cells
Virus acquires many mutations that allow it to grow well in monkey cells
Virus no longer grows well in human cells and may be candidate for vaccine

Question 17

Pros of using a live attenuated vaccine

Answer 17

Rapid broad, long lived immunity
Dose sparing
Cellular immunity

Question 18

Cons of using a live attenuated vaccine

Answer 18

Requires attenuation

May revert

Question 19

Pros of using an inactivated vaccine

Answer 19

Safe

Can be made from wild type virus

Question 20

Cons of using an inactivated vaccine

Answer 20

Frequent boosting required

High doses needed

Question 21

What types of vaccines are available for influenza?

Answer 21

Live attenuated

Purified subunit

Question 22

What types of vaccines are available for polio?

Answer 22

Live attenuated: SABIN

Inactivated: SALK

Question 23

What type of vaccine does rotavirus have?

Answer 23

Live attenuated reassortant

Question 24

How are recombinant attenuated virus vaccines made?

Answer 24

The virulence gene is either mutated or deleted

Question 25

Give 2 examples of anti-cancer subunit vaccines

Answer 25

Hepatitis B: Surface antigen cloned and expressed in yeast

HPV: Virus like particles from recombinant coat proteins

Question 26

How can we use viruses against viruses?

Answer 26

Can GM viruses to express certain proteins

Make viruses that deliver genetic material into cells

Question 27

Name 2 vaccines against Ebola

Answer 27

GSK: Chimpanzee adenovirus vectored vaccine that expresses Ebola G protein
Merck: Vesicular Stomatitis Virus vectored vaccine expressing Ebola virus G protein.

Question 28

How do Ebola vaccines work?

Answer 28

Clone Ebola G protein into other viruses that don’t cause disease
Use as vector to deliver Ebola G protein, to initiate immune response that will defend against Ebola

Question 29

How is Ebola virus treated?

Answer 29

Passive immunisation:
Zmapp
Serum therapy

Question 30

What is Zmapp?

Answer 30

Mix of 3 monoclonal antibodies raised against G protein of a previous strain of Ebola virus given as passive immunotherapy

Question 31

What is serum therapy?

Answer 31

transfer blood from survivors into other person

Question 32

3 Antiviral treatment approaches

Answer 32

Interferons to induce the hosts natural antiviral response
Drugs with specific antiviral activity
Treatment that alleviate symptoms but do not inhibit virus replication

Question 33

Antiviral treatments: Interferons

Answer 33

Enhances own natural antiviral system
On infection, cell recognises virus as being foreign, so secretes interferons
They signal to other cells to ‘ramp up’ expression of interferon stimulator genes
Protects against virus

Question 34

What are the limitations of using interferons as antiviral treatment?

Answer 34

Activates inflammation and fever

Can make the patient feel even more ill

Question 35

Why is it difficult to develop directly acting antiviral drugs?

Answer 35

Viruses mimic/ use many healthy cells, so selectivity would harm healthy cells

Question 36

What do most antiviral drugs target?

Answer 36

Viral enzymes
Often act as substrate analogues (look like enzyme substrate, but slightly different so clog enzyme)
or are cancer like drugs- nucleoside analogues (block replication)

Question 37

How do nucleoside analogues inhibit viral replication?

Answer 37

Chain termination
Modified nucleoside incorporated into DNAlacks of 3’ -OH
Prevents phosphodiester bond formation

Question 38

How is acyclovir specific?

Answer 38

Only activated inside virus infected cells

Higher affinity for viral DNA polymerase than for host cell polymerase

Question 39

Resistance to acyclovir

Answer 39

Rare but maps to thymidine kinase

Question 40

How does Neuraminidase provide a target for drugs?

Answer 40

Crystal structure of neuraminidase allows us to see how substrate binds into enzyme and how it works

Question 41

What is sialidase enzyme also known as, and what is it?

Answer 41

Neuraminidase

Spike protein on outside of influenza virus

Question 42

Name 2 drugs that inhibit Neuraminidase

Answer 42

Zanamivir

Oseltamivir

Question 43

Neuraminidase inhibitors

Answer 43

Drugs created that look like substrate (Sialic acid) but are chemically different
Bind irreversibly into enzyme active site

Question 44

Active retroviral therapy for HIV includes drugs that block:

Answer 44

Entry of HIV into cells
Early stages of infection
Integration of virus DNA into hosts DNA
Processing of proteins of virus

Question 45

Name 4 types of drugs that treat Hepatitis C

Answer 45

Protease inhibitors
N5SA
NNPI
NSSB polymerase inhibitors

Question 46

How was Hepatitis C treated for over 20 years?

Answer 46

Therapy relied on interferon treatment with ribavirin