Results of Fusion-incompetent (FI) immunogens:
Figure 2A
Reciprocal serum dilution
Transgenic mice were immunized with FC immunogen (black squares;n=4), FI immunogens(COS-env with U87 cells, gray circles,n=4; COS-env with U87-CD4 cells, gray diamonds,n=3; COS-env with sCD4, white diamonds,n=2; COS-env with U87-CD4-CCR5 cells, each fixed separately before mixing for immunization, gray squares,n=2), or mock-transfected COS cell immunogen (cocultured with U87-CD4-CCR5 cells)(white circles;n=2). Unimmunized control mice (white triangles;n=2) were also used.
___________________________________________________________________________
In the neutralization assay, cells were infected with a known amount of virus.
Figure 2A Interpretation
a) COS-env cells cocultured with U87 cells ( No CD4 or CCR5 coreceptors ) Interpret results These FI immunogens were unable to elicit significant neutralization of the homologous PI virus
b) COS-env cells cocultured with U87-CD4 cells (No CCR5 coreceptor!) Interpret results These FI immunogens were unable to elicit significant neutralization of the homologous PI virus
c) COS-env cells to which soluble CD4 (sCD4) was complexed Interpret results These FI immunogens were unable to elicit significant neutralization of the homologous PI virus
d) COS-env cells with U87-CD4-CCR5 cells that were separately fixed with formaldehyde before mixing during the formation of the vaccine Interpret results These FI immunogens were unable to elicit significant neutralization of the homologous PI virus
e) The FC immunogen (black squares on figure 2A) Interpret results In marked contrast to all the FI immunogens, the FC immunogens were able to elicit significant neutralization of the homologous PI virus.
Stop and Think: What is the difference in neutralization by FC vs. FI immunogens ( vaccine ) sera? Answer The FC vaccine presents unique fusion-dependent determinants that mediate neutralization of PI viruses. So what? The failure of the FI immunogens highlights the specificity of the neutralization elicited by FC vaccines.
Stop and Think: Based on these results, would a rgp 120 vaccine ( recombinant glycoprotein 120 ) be capable of eliciting PI virus neutralization? Answer No, this vaccine has also not been successful.
NEXT QUESTION TO PONDER:
What would be expected if the same FC and FI vaccine groups mentioned above were used in assays with human primary blood lymphocytes (PBLs)? Click here to find out!
Click here to go back to Main Menu