The effectiveness of an AIDS vaccine appears to depend on itsability to conform to the shape of viral proteins, according tofindings by Chiron Corp. scientists.
Scientists working to devise AIDS vaccines have found that theantibodies made in response to their test vaccines will notneutralize all strains of the virus, yet human antibodiescollected from infected individuals can react to a wide rangeof viral strains.
Researchers had thought that the best immune target toinclude in a vaccine is the V3 region within gp120, a protein inthe viral coating.
Yet copying the linear protein sequence of V3 is "not the wholestory," company investigator Kathelyn Steimer told BioWorld.To be widely effective, a vaccine must also present to theimmune system a sequence of amino acids that can adopt thenative conformation, or shape, of viral proteins.
In a report today in Science, the Chiron researchers purifiedantibodies from the blood of people infected with HIV, usingtwo recombinant gp120 proteins to essentially pull theantibodies that bind to them out of the blood.
The antibodies fished out by one of the recombinant gp120proteins neutralized only two HIV strains tested, butantibodies caught by the other neutralized a broader spectrumof viral strains.
Only this latter gp120 protein blocks binding of the virus toits cellular entry portal, the CD4 molecule -- an action thatrequires the protein to have the correct, folded conformation,as well as the correct sequence of amino acids.
Blood serum collected from primates immunized with multipledoses of the conformationally correct gp120 neutralizes abroad range of HIV-1 isolates, the researchers reported.
"Our version of gp120 is a good candidate for a vaccine,because it is cross-reactive" to many strains of the AIDSvirus, said Larry Kurtz, spokesman for the Emeryville, Calif.,company (NASDAQ:CHIR). The company has several patentspending on recombinant gp120 proteins as well as recombinantenvelope proteins.
The conformationally correct gp120 is glycosylated; that is, ithas sugars added to it, and is made by genetically engineeredmammalian cells. The other gp120 is made by yeast, and is notglycosylated.
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.