Molecular Target for PI Virus Neutralization

The researchers had shown that the elicitation of PI virus-neutralizing antibodies required a functional envelope-CD4-CCR5 interaction as the immunogen.

1. Could these neutralizing antibodies recognize native, nonfunctioning envelope protein as antigen? Answer Can't tell you yet...but good thinking...read on!

2. Could neutralizing antibodies be removed from FC vaccine sera on incubation with envelope protein expressed on the surface of transfected COS cells?

To answer these questions formaldehyde-fixed COS cells expressing 168P envelope protein were incubated with FC serum. The serum was then tested for PI virus neutralization.

 Figure 6: Adsorption of PI virus neutralization activity by formaldehyde-fixed COS-env cells. FC vaccine serum was repeatedly incubated with formaldehyde-fixed COS-env (gray squares) or control COS (white squares) cells. Serum obtained before FC immunization was similarly adsorbed (gray and white circles, respectively). The starting FC and preimmunization sera are indicated as black squares or black circles, respectively. Sera were tested for neutralization of 168P with U87-CD4-CXCR4 cells.

Was neutralization activity in FC vaccine serum removed by incubation with envelope-expressing cells? Answer yes

Was neutralization activity in FC vaccine serum removed by incubation with COS cell controls? Answer only minimally reduced

  Interpretation Although the static form of the envelope protein does not function as an effective immunogen, some aspects of the critical fusion-dependent epitopes are sufficiently represented on the static protein to allow binding. This initial binding to non functioning envelope protein may facilitate subsequent access of antibody to transient fusion-dependent conformations that arise during binding and fusion.

What does this data suggest in regards to the PI virus neutralizing antibodies target? Answer The PI virus neutralizing antibodies target, at least in part, the HIV envelope protein. Also the PI virus neutralizing antibodies do not target adventitious cellular proteins, which would be equally recognized ( or not recognized) on control COS cells.

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Could neutralization activity be removed by adsorption to U87-CD4-CCR5 cells?Click here to find the answer

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