A new dimension in AIDS vaccines _ literally _ is looking forcommercial money to fund clinical trials. Half a dozen rhesus monkeyshave already restored infection-blocking antibodies against what itsinventors call their "peptomer" immunogen.On July 11, the Federal Register (p. 35,376) announced that "novelconformationally constrained peptide polymer HIV vaccine candidateshave been uncovered that generate a strong humoral immune responsenot seen against monomeric peptides."The notice invites "expeditious commercialization" of the invention,for which the National Institutes of Health Office of TechnologyTransfer (OTT) filed a U.S. patent application (No. 08/184,330) on Jan.19, 1994.Its principal inventor, physical chemist Frank Robey, heads the peptideand immunochemistry unit at the National Institute of Dental Research.He told BioWorld Today that his approach "may be a rational one fordeveloping an HIV vaccine that avoids the molecular mimicry thatplagues the current vaccine strategies."He added that "Whereas all other AIDS vaccine developers have triedendless variations of sequences and synthetic modifications," hishelical peptomers are polymers carrying conformational epitopes,"designed after the capsular polysaccharides that people use asvaccines against bacteria. We took their idea and put it into the AIDSviruses, HIV-1 and HIV-2. By doing that we were able to get a peptideto take on a conformational spatial arrangement in the molecule of atleast two, probably three, dimensions."These peptomers consist of cross-linked, synthetic peptide sequencesfrom the highly conserved CD4 binding domains of HIV's gp120regions. Their conformations, Robey points out, "resemble thetheoretical conformations in these native gp120 regions.These peptide polymers display a prominent alpha-helical secondarystructure," Robey said, "which the free peptide does not."His studies show that they bind CD4, block gp 120 from binding toCD4 and elicit new antibodies in rhesus macaque monkeys pre-immunized with recombinant gp 120 and gp 160 products. "The greatbenefit of this vaccine," Robey stresses, "is that it doesn't require anadjuvant. And the new antibodies react with native protein, and blockHIV-1 infection in vitro." His monkey trials are being conducted incollaboration with the FDA's Bureau of Biologics."Multitudes of companies out there are doing AIDS vaccines," Robeysaid, "and a ton of them have been scared off, because it hasn't worked.They're shell-shocked." He added, "I can honestly and legitimately,right this minute, go into a human trial with this peptomer material --given the wherewithal."OTT, through the Federal Register, is offering to put the product'sintellectual property protection on the licensing block, to obtain theneeded financial resources.When Robey adds, "I know the FDA would approve an investigationalnew drug application," he knows whereof he speaks. During the 1970s,he spent eight years in the agency's Bureau of Biologics, and wrote thechemical part of the original "Points to Consider" for productsproduced by recombinant DNA technology.(Editor's Note: For licensing information, contact OTT contractspecialist Steven Ferguson at (301) 496-7735, extension 266.) n
-- David N. Leff Science Editor
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