Therion Biologics Corp. announced Tuesday that its prophylacticAIDS vaccine, TBC-3B, is entering Phase I trials at four U.S.sites. The study is being funded and conducted by the NationalInstitute of Allergy and Infectious Diseases (NIAID) and willevaluate the agent's safety and immunogenicity in 50 healthyvolunteers.
The vaccine is being developed for the prevention of AIDS inhealthy people. According to Therion's president and chiefexecutive officer, Dennis Panicali, TBC-3B represents a uniqueapproach to neutralizing HIV because it is based on multipleproteins within the virus, producing both antibody and cell-mediated responses. The vaccine is based on a recombinantvaccina viral vector that contains the major structural and non-structural proteins of HIV. These include the matrix (p 17),core (p 24), envelope (gp120 and gp41), nucleocapsid (p 7),reverse transcriptase, integrase and protease antigens.
Panicali believes the Cambridge, Mass., company's multipleprotein approach will obviate the need to develop vaccinesagainst various strains of the virus. While the non-structural(e.g., envelope) proteins of HIV tend to change among variousstrains and can even mutate within the body, the structuralproteins of the virus (e.g., matrix, core, nucleocapsid andreverse transcriptase) remain relatively intact betweendifferent virus strains, Panicali said.
At present, the company's vaccine contains proteins derivedfrom a common North American strain of HIV, which it hopeswill be effective for most patients. If the envelope proteinshave mutated or come from a different strain, Panicaliexplained, Therion believes the structural antigens will stillneutralize the virus. In the future, he added, the company maydevelop a vaccine specifically targeted at other common strainsof HIV.
Another advantage of Therion's vaccine, according to Panicali,is that it has shown preclinical efficacy in eliciting both anantigen response against free-floating HIV in the blood streamand a cell-meditated response against virus contained withincells. The vast majority of HIV infection, he noted, is withininfected cells, and is thus inaccessible to antibodies. Aneffective vaccine, he said, must elicit cytotoxic T cells -- whiteblood cells that destroy virus-laden cells.
Panicali said he is not aware of any other company using amultiple protein approach in the development of an AIDSvaccine, although United Biologicals Inc. is developing a vaccinetargeted at several strains of the virus.
In Phase II and III trials, Panicali said, the company willexamine the agent's efficacy by giving it or placebo to membersof the large high-risk population and will determine its efficacyby tracking respective infection rates. The current trial, whichwill last about 18 months, is being conducted at St. LouisUniversity School of Medicine, the University of RochesterMedical Center, in Rochester, N.Y., the University of WashingtonPacific Medical Center in Seattle and Vanderbilt UniversityMedical Center in Nashville, Tenn.
-- Karl A. Thiel Business Editor
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