Antiviral vaccines & chemotherapy

Question 1

What is the difference between passive and active immunisation?

Answer 1

Passive: Given Aby = neutralise Ag (e.g. toxin). I.Sys not involved = short term protection
Active: Given Ag = I.sys involved = make Aby. Long term protection (-prophylaxis)

Question 2

How are viruses attenuated?

Answer 2

• removal of virulent genes
• modify growth cond.: temp, lo [O2], substances in growth media

Question 3

a) why are adjuvants used?
b) Describe the actions of adjuvants

Answer 3

a) enhance immunogenicity to vaccine
b) stimulate innate immune resp -> initiate adaptive immune resp

Question 4

What are the advantages of the mRNA and Adenovirus vaccines.

Answer 4

• stimulate immune response
• no Adjuvant needed
• NA not integrated in host genome

Question 5

What are “Prodrugs” and what advantages do they have?

Answer 5

• have chemical side group on antiviral molecule > activates the antiviral when profrug is cleaved by host enz
  = enhance adsorption & tiss penetration to oral drugs

Question 6

Aciclovir is active in cells infected by Herpes viruses and not in uninfected cells. Why?
*note infected cells must be dividing

Answer 6

Herpes-infected cells have herpes thymidine kinase that phosphorolates drug -> monophosphate -> triphosphate = active agent -> binds & inhibits herpes V DNA pol.
* also once drug is phosphorylated can’t escape cell
Uninfected cells don’t have enz.

Question 7

What are the current anti HCV drugs directed against, how do they work?

Answer 7

• Daclatasvir, ledipasvir, omitasvir: NS5a = *RNA dependent RNA pol
• Sofosbuvir: NS5b *RNA dependent RNA pol
• Paritaprevir, Ritonavir?: NS3/4a = protease inhibitor

Question 8

Describe the action of Amantadine in influenza infections.

Answer 8

• Bind to M2 protein = block ion channel = H+ not enter virus = no dec in pH = no uncoating of virus = not release RNA = no replication in host cell nucleus

Question 9

What is HAART?

Answer 9

Highly active anti-viral therapy
- combination of chemotherapy drugs (against HIV)

Question 10

What anti COVID drugs are used in Australia? What are the actions of these drugs?

Answer 10

• Nirmatrelvir/Ritonavir: Protease inhibitors = prevent peptide cleaving
• Molnupiravir/Lageviro: Induces copy errors during RNA replication (lethal mutagenesis)

Question 11

Briefly explain the role/mechanism of interferons as anti viral agents.

Answer 11

1. When virus infects host cell, interferon genes turned on => interferon made. Cell dies
2. Interferon stimulates production of antiviral protein in another cell
3. Antiviral proteins block reproduction in that cell

Question 12

Describe the action of AZT (Zidovudine) on HIV.

Answer 12

1. In un&infected cells, AZT phosphorylated => active triphosphate form
2. bind & inhibit RVS transcriptase ≠ RVS transcription
   .2. Stop nucleotide addition = Prevents NA elongation
   *Can be toxic since also effect uninfected cells

Question 13

Describe the actions of Fomivirsen & site administered to in treatment of __

Answer 13

• ssDNA complementary to viral mRNA = prevent translation
• administered to eye = treat CMV retinititis

Question 14

When is Dexamethasone administered for COVID19 & what it does

Answer 14

• Given LATE in disease for pts struggling to breathe
• Immunosuppressive = stops cytokine storm
  *counterproductive if used early

Question 15

When is Remdesivir administered for COVID19 & what it does

Answer 15

• Effective in Early infection (& used for Ebola V)
• Stops RNA extension/replication

Question 16

What is REGEN COV2 for COVID19 & what it does

Answer 16

2 monoclonal Aby:
- REGN10933 (casirivimab): bind to S1 = prevent attachment
- REGN10987 (imdevimab): bind to S2 = prevent fusion (b/w viral & host memb = not enter)

Question 17

The differences b/w inactivated & live attenuated vaccine in traditional vaccines

Answer 17

1. Inactivated vaccines (killed virus)
   - Have antigenicity w/out ability to infect, but require adjuvants
   - Make Aby against envelope / capsid proteins
2. Live attenuated
   - Alive but lost ability to cause disease & usually not require adjuvants
   - more successful bc mimics real infection
   - risk of causing infection

Question 18

Describe these 3 protein vaccines
a) Subunit vaccines
b) Synthetic vaccines
c) Virus like particles (HPV)

Answer 18

a) isolating a protein / carbo from virus that illicit good I.Resp.
b) 1º structure of proteins & peptide chains but may not be recognised by I.Sys
c) Just use capsomere w/out DNA/RNA
*All require adjuvants

Question 19

Describe these 3 Gene-based vaccines
a) Viral vectors
b) mRNA vaccines
c) Gene vaccines

Answer 19

a) Stimulate I.Resp w/out adjuvant & DNA not integrate in host genome e.g. adenovirus vector carrying spike protein DNA sequ.
b) mRNA vaccine in lipid nanoparticle - can stimul. I.Resp. *Heat labile
c) Inject viral genes directly onto muscle / skin = expression on cell surface

Question 20

5 Ideal features for a vaccine

Answer 20

• Effective: provide protective immunity over durtion
• Available: produce lrg supply
• Stable (w/ temp, humidity) e.g. mRNA is heat labile
• Cost
• Safety (no adverse side effects)

Question 21

a) chemotherapeutic index equation
b) range of effective drugs

Answer 21

a) = inhibitory dose ÷ toxic dose
b) 100-1000

Question 22

6 point of actions for antivirals

Answer 22

• Bind to free viral particle
• Interfere w/ V adsorption (binding to rceptor)
• Inhibit V coating
• Inhibit viral transcription & replication e.g. RNA dependent RNA polymerase
• Disrupt cell. processing of viral particles (but cellular proteins might be similar to host = damage)
• Interfere w/ V maturation or budding: inhibt release of virus