By David N. LeffScience Editor

Paradoxically, an AIDS patient's own antibodies get in the way ofmeasuring how far his or her HIV infection has progressed. Currenttests to detect the virus in blood plasma assay p24, an antigen in theviral core.

This antigen-capture assay, at present the only such test in town, islargely frustrated by redundant antibodies, said retrovirologist LarryArthur. He directs the AIDS vaccine program at San Diego-basedScience Applications International Corp., which manages theNational Cancer Institute's Research and Development Center inFrederick, Md., under contract.

"The problem you run into," Arthur told BioWorld Today, "is thatinfected people develop a really good antibody to the p24, and thatinterferes with the assay." P24, he noted, "is one of the predominantmolecules in the human immunodeficiency virus. It's a capsid proteinthat sits in the interior of the virion."

Arthur and his associate, Louis Henderson, have screened over 1,000AIDS patients and found that almost none of them raise suchnuisance antibodies to another major HIV protein, p7, which isapparently involved in packaging the viral genomic RNA. They havedevised a prototype nucleocapsid capture test based on p7 instead ofp24, which NCI has filed to patent (under Serial No. 07/967,658,dated Oct. 28, 1992).

Patent Licensure Up For Non-Exclusive Grabs

A notice in the March 31 Federal Register invites industrialapplicants for non-exclusive, worldwide, royalty-bearing licenses todevelop and commercialize the assay.

"We actually capture the protein," Arthur explained. "That means,instead of attaching an antigen to the 96-well plate for the antibody tobind to, we attach an antibody, which captures the antigen out of theplasma."

He pointed out that "there is a correlation between progression toAIDS and the amount of virus in a person's blood."

Besides antibody interference, he said, current systems are difficult todeploy in a clinical setting, what with the difficulty of usingpolymerase chain reaction. "This is why current viremia assaysmostly use antigen-capture detection in plasma."

Arthur has compared virus detection in the p24 and p7 capture assaysin blood from AIDS patients. "What happens is," he explained,"when you take the plasma, you have to lyse the virus in order torelease the proteins for the assay. At that lysis procedure," he added,"soluble antibodies to p24 will bind to those molecules, and makethem unavailable to the capture antibodies. With p7, since there arefew if any antibodies, we don't seem to have that problem." Headded, "This makes p7 an ideal candidate for an HIV screeningassay."

Potential clinical uses of measuring p7 concentration in bodily fluidsinclude prognosis of disease, determining if a person vaccinatedagainst HIV-1 is or is not infected, and detecting infection in infantsborn to HIV-infected mothers.

Igen In The Running For R & D Rights

"There is also a correlation," Arthur added, "between theeffectiveness of antiviral agents and whether they can decrease theamount of virus in the plasma of an infected patient. We've devisedassays to screen anti-HIV drugs, such as AZT, against thenucleocapsid protein. This will be available later in a separatelicensing offer to industry."

Arthur already has done some preliminary experiments on his p7nucleocapsid-capture test with scientists at Igen, Inc. of Rockville,Md. "They have electrochemoluminescence technology," he said, andjust in preliminary work have been able to enhance the assaysignificantly.

"We sent them reagents, antisera and p7," Arthur continued, "andthey determined the lowest level of p7 they could measure in theirchemoluminescence assay. It came down to about four picograms permilliliter. That perhaps is a little bit more sensitive than thecommercially available p24 capture.

"Igen is very much in the running for a license, non-exclusivebecause their technology is different from others," Arthur said. "Theywere waiting for our offer to be announced in the Federal Register."

Editor's Note: For patent licensing information, consult StevenFerguson, NIH Office of Technology Transfer, (301) 496-7735, ext.287; for technical questions concerning this invention, Cindy Fuchs,(301) 846-1501. n

(c) 1997 American Health Consultants. All rights reserved.