A small biotech company in Alexandria, Va., Cel-Sci Corp. by name,asserts that its AIDS vaccine, unlike all others, is barking up the righttree.
Its clinical trial data, Cel-Sci CEO Geert Kersten told BioWorldToday, "will show that [HIV vaccine] people are essentially lookingat the wrong correlates of cellular immune responses."
Harking back to the slump in enthusiasm for AIDS vaccines, whichhad peaked a little over a year ago, Kersten said, "What failed inthose days was essentially one approach _ the viral envelope proteinapproach."
Virtually all players in the AIDS vaccine game, Kersten observed,have played only cards counting on antigens in HIV's outer envelopeas winners. That house of cards tottered when it turned out that thosegp envelope proteins mutated rapidly, presenting ever-new antigensto foil experimental vaccines.
"Our vaccine," Kersten explained, "focuses on a protein, p17, in theviral core, not its outer shell. And the beauty of p17 is that it's a piecethat shows much less variation."
Putting that postulate to the test, Cel-Sci scientists injected virulentinfective HIV-1 virions into 50 mice. The deadly dose each receivedwas 10,000 times greater than what would normally infect a mouse.
Three days earlier, those SCID mice (devoid of murine immunedefenses) were injected with 20 million peripheral blood lymphocytesfrom healthy seronegative individuals who previously had beeninoculated with Cel-Sci's p17-based synthetic vaccine, HGP-30.
These five human volunteers received a starter injection of HGP-30vaccine in 1991, and booster shots in 1995. The mouse experimentaimed at testing their immune resistance to the virus.
On Sunday morning, those at the 10th annual Conference on ClinicalImmunology meeting in New Orleans, on the margin of the largerFederation of American Societies of Experimental Biology conclave,heard how the in vivo experiment had fared.
James Talmadge, of the University of Nebraska Medical Center inOmaha, told his audience that 39 of the 50 mice (78 percent) did notcontract HIV infection, whereas only four of 30 control animals (13percent) escaped it. Those 30 controls had been injected with bloodcells from human volunteers who did not get the HGP-30 vaccine.
Strikingly, the viral challenge to the animals was from a differentstrain than the strain on which the sequence of the vaccine's antigenis based.
Talmadge told BioWorld Today that the experimental pathologylaboratory in Omaha had carried out the analyses under continuingcontract to Cel-Sci, for which he is principal investigator.
HIV's p17 core protein is the 130-amino-acid product of itsnucleocapsid gag gene. Virologist Pram Sarin, vice-president ofresearch at Cel-Sci and its subsidiary, Viral Technologies Inc., toldBioWorld Today that the protein comprises the HIV virion'sstructural matrix, just inside the envelope, and is essential to viralreplication.
Sarin co-invented the HGP-30 molecule a decade ago by trimmingthis sequence down to the 30 amino acids that made up the mosthighly conserved _ least mutation-prone _ region, and containingepitopes attractive to the human cellular immune system's cytotoxicT lymphocytes. "These CTLs," Sarin explained, "are what kill thevirus-infected cells."
AIDS specialist James Kahn, of San Francisco General Hospital, anda clinical collaborator of Cel-Sci, has submitted an abstractelucidating the vaccine's CTL-triggering mechanism to the 11thInternational Conference on AIDS meeting next month in Vancouver,British Columbia.
Asked why Cel-Sci alone of all the dozen or more biotech firmsengaged in developing AIDS vaccines had turned from envelope tocore antigens, Sarin replied, "For the simple reason they have apatent on it."
Cel-Sci is a publicly owned company, which, Kersten said, has raisedabout $5 million so far this year.
Early next year it expects to complete a Phase I/II clinical trial thatgot under way last November, in collaboration with AIDSReSEARCH Alliance, of West Hollywood, Calif.
"We are almost fully enrolled in this study," Cel-Sci's vice presidentof regulatory affairs, Douglas Winship, told BioWorld Today. "It willinclude 22 volunteers, all supposedly asymptomatic, otherwisehealthy and HIV-1-infected. It's supposed to be a safety study," headded, "but we are monitoring viral load and CD4 counts.
"The 22 subjects consist of two groups, divided by their CD4 levels.The majority of them, 16, have counts between 300 and 750. Theremaining six range from about 50 to less than 300."
Winship observed that "in this latter group, we wouldn't necessarilyexpect to see an immune response, but if we do, it could be helpful tothem."
So far, Cel-Sci sees its HGP (human gag protein) vaccine astherapeutic rather than preventive. "Our original idea," Kersten said,"was for both. But we need a partner to develop it as a prophylacticvaccine. It's too big an undertaking for us to go it alone. We'vetalked with a few people, but it's very early on." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.