MbShea@PWP@English@UMCP

Madeleine Mankowski

Abstract:

Although the existence of broadly neutralizing monoclonal antibodies (bNmAbs) against hepatitis C virus (HCV) is well established, the interactions between pairs of bNmAbs have not yet been systematically evaluated.

HCV variants that are naturally resistant to described bNmAbs have been identified by multiple studies. Such resistance makes it probable that a single bNmAb would not offer sufficient protection against exposure to multiple HCV quasispecies. Since human antibody responses to HCV are naturally polyclonal, a vaccine that stimulates multiple bNmAbs could provide a solution to the observed viral resistance.

bNmAbs have previously been grouped into three different clusters based upon their neutralization profiles. The two main clusters have complementary neutralization profiles; therefore, combining antibodies from each cluster should cause an increased response to viral challenges by expanding both neutralization breadth and overall neutralization.

In this study, the exact interactions between anti-HCV bNmAbs in the presence of HCV quasispecies were systematically quantified. A screen in which 15 bNmAbs were tested in various combinations against a panel of 11 HCV pseudoparticles was used to identify combinations with potential synergy. Three potentially synergistic combinations were further analyzed using Combination Index (CI), Degree of Independence (DI), Loewe Additivity, and Bliss Independence. Though an overall increase in total average neutralization was seen in all combinations, none of the combinations were found to exhibit true synergism. One combination (mAb1 & mAb2) was found to have interactions mimicking those predicted by the Bliss Independence model, indicating that mAb1 & mAb2 would be ideal targets for an antibody vaccine.


Word Count: 250


Reader’s Profile: I imagine a difficult reader in a scientist who has done similar studies but used only CI to quantify his or her results.


Reader’s Response: Why is CI not used as the major method of analysis of antibody interactions in this paper? CI is a well-established method that has been used that has been used for all previous studies of anti-HCV mAb* combinations. I myself used CI to analyze the interactions between mAbs just a couple of years ago. It seems as though she is saying my previous conclusions were incorrect. Sounds like I shouldn’t bother reading this paper.

*monoclonal antibody

M -- good understanding of methods as being a place where scientists of good will and powerful intellect can disagree

:)