Lecture 6- Prevention and treatment of viral disease Flashcards
What is the difference prophylaxis and therapy?
PROPHYLAXIS= preventing the disease before the etiological agent is acquired by vaccination or prophylactic drugs
THERAPY+ tranig disease after infection of host
What are the two mechanisms of defence against viruses?
Vaccines- prophylactic
Antiviral drugs- Therapeutic
Why was the smallpox vaccine lead to the eradication of smallpox?
- No animal reservoir
- No latent or persistent infection
- easily recognisable disease
- vaccine effective against all strains
- Properties of vaccine: potency, low cost, abundance, heat stability, easy administration
What are the different types of vaccines? Give examples of viruses along with them
- live attenuated virus vaccine (influenza, MMR, Polio, smallpox, varicella)
- inactivated virus vaccine (HepA, Rabies, Japanese encephalitis)
- Fractionates subunit vaccine ( Influenza)
- live virus vector vaccine
- DNA vaccine
How do you generate an attenuated virus?
1) Pathogenic virus isolated from patient and grown in human cultured cells
2) Virus used to infect permissive cell line (monkey cells)
3) Virus mutates and evolves exclusively to monkey cells
4) Virus can’t grow in human cells =vaccine
What are the pros and cons of a live vaccine?
PROS: - rapid, broad ,long lived immunity - dose sparing - cellular immunity CONS: - requires attenuation - may revert
How are inactivated vaccines generated?
- Destroy genome
- host has immune response to virus surface proteins
What are the pros and cons of inactivated vaccines?
PROS: - safe - can be made from wild the virus CONS: - needs frequent boosting - high doses needed
Which two viruses have both live and attenuated vaccines?
Influenza
Poliovirus
What are the two forms of the poliovirus?
- Salk inactivated vaccine
- Sabin live attenuated vaccine (not for immunocompromised individuals)
What are the two forms of the influenza vaccine?
- Inactivated virus/ HA subunit
- LAIV (FluMIST)- for children
How are recombinant attenuated virus vaccines synthesised?
- remove gene for virulence
- gene for receptor binding proteins and capsid remains
- immuogen but not pathogenic
What sort of vaccine is rotatrix and which virus is it used against?
Rotavirus (death by diarrhoea and vomitting)
- live attenuated rotavirus recombinant vaccine
What are the criteria for administering rotatrix?
- Can cause intussusception (bowel blockage) in babies older than 3 months
- only given to babies under 15 weeks
Name some subunit vaccines, the subunit they contain and the virus they target
1) Gardasil and Cervarix–> papilomavirus–> virus like particles from recombinant coat proteins
2) HBV vaccine –> Hep B –> sAG cloned and expressed in yeast
What sort of vaccine is the shingles vaccine and who is it administered to?
Live attenuated vaccine
- for those aged 70 or 79
What might vector Ebola G proteins in the Ebola vaccine?
Chimpanzee adenovirus
VSV
What are the three different types of antiviral treatments?
1) Interferons to induce the hosts natural antiviral response
2) Drugs with specific antiviral capacity
3) Treatment to alleviate symptoms
Name a specific group of antiviral drug and briefly describe how they work
Nucleoside analogues
- nucleoside incorporated into DNA
- lacks 3’ OH
- prevents phosphodiester bond formation
Name a specific nucleoside analogue and briefly describe its mechanism of action
Acyclovir
- activated in virus infected cells
- higher affinity for Viral DNA polymerase than host cell polymerase
- maps to thymidine kinase
Name the antivirals used against influenza
Amantadine, Zanamivir, oseltamivir
Name another group of antivirals and how they work. Give a couple of examples of antivirals within this group
Neuraminidase inhibitors (NA are influenza surface proteins which cleave sialic acid and allow the exit of influenza from its hot cell) - sialic acid, relents, tamiflu
What are the different stages of the HIV replication cycle that antivirals target?
1) Binding and ENTRY inhibitors
2) REVERSE TRANSCRIPTION inhibitors
3) INTEGRATION inhibitors
4) Transcription and translation to proteins (PROTEASE inhibitors)
5) Transcription to replicate genome
6) Virion assembly
7) Budding and exit
What was the initial treatment for HCV? what were the disadvantages of this treatment?
- Interferon treatment wit ribavirin
- only effective in 50% patients
- unpleasant side effects
What were the two drugs which developed against HCV? what were the consequences of it?
Protease inhibitors- telaprivir and boceprivir
–> resistant mutants generated by monotherap y –> Combination therapy with IFN and RBVN
What is the immunisation strategy for ebola?
1) vector vacine: G protein carried on a different virus
2) Passive vaccine
- Zmapp (3 MABs)
- Serum therapy from survivors
