Exam III: Bavituimab Paper

Question 1

What was the general purpose behind the paper?

Answer 1

Need for antivirals that work against multiple classes of viruses = “broad spectrum” antivirals

Question 2

What is phosphatidylserine (PS)?

Answer 2

The most abundant phospholipid normally on the internal side of the plasma membrane

Question 3

Why was PS the target of their antibody?

Answer 3

PS is normally on the inside of cells

But viral replication and apoptosis can cause the PS to present on the outside of the cell

Question 4

What are the specifics of how PS and other anionic phospholipids are expressed intracellularly starting with viral infection?

Answer 4

Viral infection > increase in intracellular Ca > PS exporter expression + inhibition of translocase > PS expressed extracellularly

Question 5

How does Bavituximab work?

Answer 5

Binds to phosphatidylserine via the Beta2GP1

Question 6

Why did Bavituximab need to be chimeric?

Answer 6

Need the human antibody to alert our immune system

Need the mouse antibody to bind to phosphatidylserine

Question 7

What is the genome of the pichinde virus? Why did the researchers use it?

Answer 7

Enveloped
negative ssRNA
Guinea pig equivalent of Lassa fever virus in humans

Question 8

How do you test to see if the antibody is binding to the virus?

Answer 8

Flow cytometry

The further to the right the peak is = the higher the presence of antibody

Question 9

What does MFI stand for?

Answer 9

Mean Flourescencse Intensity

Question 10

How to test for the location/translocation of antibody?

Answer 10

Attach flourescence to antibody

Question 11

ELISA Assay

Answer 11

Plates coated with antibody of interest > wash plates with virus > wash with antibody against virus > wash with secondary antibody > wash with substrate > produces color

Question 12

Bead depletion study

Answer 12

Magnetic beads coated iwth antibody of interested > put in tube of virus > what percentage of virus was removed from the tube

Question 13

Kaplan Meier Survival Curve

Answer 13

Survival as a function of time after infection

Question 14

What is the Ribavirin mechanism of action?

Answer 14

Ribavirin = guanosine nucleoside analogue > inserts itself into viral RNA by tricking the RDRP > halts the transcription when RNA polymerase get there because it doesn’t know what to do

Question 15

What are the protective effects of Bavituximab?

Answer 15

1. Opsonization and clearance

2. Antibody-dependent cell cytotoxicity

Question 16

PS is common in ____ which are commonly found on viral envelopes due to the way they bud out of the cell membrane

Answer 16

rafts

Question 17

What negative effect does PS exposure have for viruses?

Answer 17

PS exposure can sometimes means “I’m already undergoing apoptosis, don’t send over the immune system because there is nothing to worry about” and when viruses have ti - they evade the immune system

Question 18

Blood coagulation times can provide information about how well tolerated the antibody is

Answer 18

True