CW HENDERSON PUBLISHER -- Heat inactivation appears to increase the antigenicity of HIV, possibly by exposing previously hidden epitopes. The finding comes from a research team using an all-but-abandoned approach to creating an AIDS vaccine: inactivated whole virus.
Early efforts to create an inactivated SIV prototype vaccine were abandoned after early failures. There have been few efforts to revive this time-honored approach to creating vaccines. But now the concept has come back with astonishing results.
"We found we could maintain or increase the antigenicity of HIV," reported Kathie Grovit-Ferbas of the University of California, Los Angeles. "Heat inactivation increased the presence of normally cryptic CD4 binding epitopes."
Grovit-Ferbas reported the findings in a presentation to the Second Annual Conference on Vaccine Research, held March 28-30, 1999, in Bethesda, Maryland.
Normally, HIV tends to shed its envelope when inactivated. But the researchers, working in collaboration with Acrogen, Oakland, California, found that their inactivation technique avoided this difficulty.
"Our results indicate that relatively simple processes involving thermal and chemical inactivation can inactivate HIV-1 by at least 7 logs and maintain envelope glycoproteins on the virion surface in a strain-dependent fashion," Grovit-Ferbas and colleagues reported in their presentation abstract.
In a demonstration of the real-world relevance of their vaccine prototype, they showed that their inactivated HIV can be presented by dendritic cells to drive cell-mediated immune responses in peripheral blood mononuclear cells (PBMC) obtained from HIV infected donors.
"We will also look at an autologous virus system to inactivate virus from patients for possible immunotherapy," Grovit-Ferbas said.
Meanwhile, she and co-workers are conducting small-animal immunogenicity studies of the vaccine.