Vaccines and Antivirals

Question 1

Who is credited with the creation of the first vaccine?

Answer 1

Edward Jenner - Cowpox

Question 2

name at least 3 types of anti-viral vaccines

Answer 2

Live WT virus (cross-species protection)
Live attenuated virus (reduced virulence)
inactivated virus (Ag only)
subunit vaccines (viral proteins only)
DNA vaccines (express immunogenic viral proteins)
Recombinant viruses (more immunogenic)
Chimeric (benign microbe with immunogenic prots)

Question 3

What two things do all vaccines require?

Answer 3

Antigen from viral protein and adjuvant which stimulates innate immunity

Question 4

Describe the antigen and adjuvant in live attenuated vaccines.

Answer 4

Antigen is viral proteins of virion and adjuvant is the viral RNA/DNA

Question 5

Describe the antigen and adjuvant in subunit vaccines.

Answer 5

Antigen is recombinant viral proteins and adjuvant is alum

Question 6

Describe alum.

Answer 6

The most common adjuvant used in human vaccines. Initiates strong Th2 response but ineffective against pathogens that require Th1 immunity.

Question 7

Describe vaccine discovery vs development time over the years.

Answer 7

Used to be long discovery and shorter development.
Morphed to shorter discovery and much longer development.
Now same short discovery but slightly mid range development.

Question 8

Describe the #__ stages of vaccine development.

Answer 8

3 stages

1: Safety w under 100 participants
2: Experimental tx for testing delivery/efficacy
3: tx to confirm efficacy vs. current therapies and side effects (1000-3000 participants)

Question 9

Name on successful vaccine and one disaster.

Answer 9

HBV subunit vaccine is great. RSV vaccine was horrid.

Question 10

Describe the successful HBV subunit vaccine.

Answer 10

Has HBV viral envelope protein which had been produced by yeast cells. Adjuvant is alum. Gives life-long protection against HBV.

Question 11

Describe the disastrous RSV vaccine

Answer 11

Formalin-inactivated RSV virus was tested on infants in 1960s and failed to protect. Induced exaggerated clinical response and involved deaths.

Question 12

Name some ways people have attempted to create an HIV vaccine.

Answer 12

Whole inactivated, live attenuated, recombinant sub-unit, synthetic peptides, recombinant viral vector, DNA, broadly neutralizing antibodies, virus like particles, recombinant bacterial vectors.

Question 13

Describe ARVs

Answer 13

Target multiple steps of viral replication
Specific to family of viruses
Must be safe but side effects are common

Question 14

Name some types of ARVs

Answer 14

Inhibitors of viral entry, uncoating, enzymes
nucleoside/tide mimics
drugs that promote anti-viral responses

Question 15

Describe HAART

Answer 15

cocktail of ARVs
Replaced AZT
Mortality due to AIDS decreased by half since HAART

Question 16

Name some anti-retrovirals in HAART

Answer 16

Nucleoside RT inhibitors (NRTIs)
Non-nucleoside RT inhibitors (NNRTIs)
Protease inhibitors (PIs)
Integrase inhibitors (IIs)
Fusion inhibitors (FIs)
Chemokine receptor agonists (CRAs)

Question 17

Describe AZT

Answer 17

Anti RT drug.
Phosphoylated intracellularly by thymidine kinase
thymidylate kinase inhibited by AZT
Nucleoside diphosphate kinase

Question 18

Describe Nucleoside Reverse transcriptase inhibitors

Answer 18

in corporated in to DNA in RT and causes chain termination.

Question 19

Describe Non-nucleoside reverse transcriptase inhibitors

Answer 19

NNRTI binds to RT enzyme usually near active site and causes structural change that disrupts the active site and leads to impaired polymerization activity.

Question 20

Describe protease inhibitors

Answer 20

binds directly to the active site of protease enzyme causing enzyme to lock and prevents cleavage of substrate.

Question 21

Describe integrase inhibitors

Answer 21

Binds to viral integrase and prevents DNA transfer function that inserts viral DNA into host chromosome DNA

Question 22

Describe fusion inhibitors

Answer 22

disrupts the interaction betwen HR1 and HR2 domains of gp41 so viral envelope fails to fuse with cell membrane.

Question 23

Why are deaths plateaued after the impact of HAART? Are we failing?

Answer 23

Not necessarily. Because HIV is so mutational it is difficult to get to it. The plateau shows that it changes so often that we have to keep up.