Tranzyme Inc announced that researchers at the University of Alabama at Birmingham (UAB) have developed a novel assay that may lead to an AIDS vaccine capable of eliciting neutralizing antibodies (NAb) that are more effective at blocking HIV-1 infection. This new assay is based upon a sensitive recombinant reporter cell-line developed by Tranzyme that permits efficient entry and replication of HIV-1.
Neutralizing antibodies are critically important as an effective human immune response by binding to and inactivating invading pathogens. Despite many years of intensive research, the role of NAb in controlling HIV-1 infection has remained unclear. The cell-line developed by Tranzyme is an effective analytical tool that promises to transform both drug discovery and vaccine development in this area.
The significance of this new technology is reported in a paper published this week in the journal Nature (March 20, 2003), entitled, "Antibody neutralization and escape by HIV-1". The paper's senior author is Dr. George M. Shaw, Professor of Medicine at UAB and Investigator at the Howard Hughes Medical Institute. His team of researchers demonstrated in patients with acute HIV-1 infection how NAb can exert sufficient viral inhibitory activity to cause complete replacement of neutralization sensitive virus by successive populations of resistant virus. Detailed molecular genetic analysis of resistant viruses led the UAB team of researchers to postulate an evolving "glycan shield" mechanism of neutralization escape whereby selected changes in glycan packing prevent NAb binding.
"The evolving glycan shield thus represents a novel mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire," said Dr. Shaw. "Using the new recombinant cell-based assay approach, we have discovered an important mechanism of how HIV-1 escapes the body's attempt to remove the virus using neutralizing antibodies. This new approach for measuring antibodies against HIV-1 will likely help develop effective vaccines against AIDS."
"These are very exciting data and may provide insights into how HIV-1 evades NAb's over time," said John C. Kappes, Professor of Medicine at UAB, and a founder of Tranzyme. Dr. Kappes, along with Tranzyme co-founder Dr. Xiaoyun Wu are both co-authors of Nature publication, and played a key role in the development of the cell-line (named JC53-bl). Dr. Kappes added, "The utility of this cell-line has been recognized for some time in the AIDS research community, and Tranzyme has supplied it freely to academic researchers." Recently, Tranzyme placed the cell-line in the NIH AIDS Research and Reference Reagent Program to facilitate the availability of the cells to international AIDS research community for academic use. The cell-line has been renamed TZM-bl.
"It's such a unique cell-line that many academic HIV researchers and pharmaceutical companies around the world have requested it," said Vipin K. Garg, President & CEO of Tranzyme. "The cell-line is available for commercial purposes for a nominal licensing fee. In fact, Tranzyme has already begun granting non-exclusive licenses for the cell-line to biotechnology and pharmaceutical companies around the world."