The anti-flagellar? Unfortunately, flagellar antigens that elicit protective antibodies are about as variable, bug-to-bug, as are LPS-determined O-side chain determinants. That is particularly true for Proteus.
It's a useless curiosity.
- g -
Worse, the U.S. patent issued with just one lousy claim relating to serotype-specific MAbs for Proteus. The European and Japanese patents issued with all claims intact, however, and one could actually cover Pseudomonas with a few MAbs. The claims cover flagellar antigens for any microorganism, in the event that you have a parasite in mind.
No, the CNTO and XOMA MAbs failed, IMO, because they had absolutely zip to do with endotoxin or Gram-negatives. The concept was that MAbs could be raised that react with the invariant core (or "KDO") region of the LPS molecule. Never seen one that has passed my filter. There may be some that are "real", but E5 and HA-1A aren't among them, IMO. There actually is a MAb that recognizes a core determinant that is shared by all [tested] Pseudomonas isolates.... it's a no BS antibody, good affinity in a variety of physiologically relevant buffers and fluids. It's the one that I went to Cambridge to talk to Greg Winter about. Last I knew he was planning to humanize it, but I never heard anything more about it. When I found out about the "B cell" patent that GNE had licensed, I assumed that they had switched the anti-Pseudomonas MAb for the CD5 reagent, H65 (CD5 is found at low density on at least a subpopulation of B cells). I didn't know about the independent work from Santa Monica (Ingene?), until you told me about it just recently.
The Proteus MAb is a kick. It's not opsonizing, and it works great for certain injury models. However, it doesn't do squat if bug challenge is I.P. More fun?...... if you impregnate agar with the MAb and then stab with Proteus, the colony grows straight up into the air off of the plate instead of swarming.
It just immobilizes the suckers until, presumably, phagocytes come in and gobble. Put the bugs i.p., where flagella are not a big pathogenesis factor, and you have a lethal infection just as though you had administered saline.
It was a real shock.... my background was the polymorphism of the MHC, and I inherited "MAbs" made by M.D.s that had never touched a multiwell plate. Sad days for biotech.
Moreover, we (at Bayer/Cutter) had licensed HA-1A from Stanford before CNTO ever knew that it existed. Between the serology in my labs and the sensitive tests that Mike Collins had established, we declared it no better than saline and returned it. As you know, it later became a focus of intense patent litigation. The CNTO trials were later halted when it was determined that HA-1A recipients were dying more frequently than placebo controls. |
