Seeking to understand the relationship between previous neutralizing antibodies to Ad5 and Ad5-specific T-cell responses, the team, headed by Michael R. Betts, Ph.D., of the University of Pennsylvania School of Medicine Department of Microbiology, Center for AIDS Research, and Wistar Institute Vaccine Center, analyzed blood samples from 40 healthy participants in the phase I safety trial of the STEP HIV vaccine for immune response to Ad5 particles. The blood samples, which came from individuals with both high and low nAb titers and thus varying degrees of pre-existing neutralizing antibodies to Ad5, had been taken from participants at baseline, before administration of the Ad5 vector vaccine under study. From their current Ad5 assay, the team found no correlation between nAb titers at baseline and CD4 T-cell frequency.
"Ad-specific CD4 T-cells are exceptionally common in humans, regardless of the level of neutralizing antibodies to Ad5," says Betts. "This is probably the major factor that disproves the main hypothesis proposed to explain the STEP trial results."
The team next questioned whether the Ad5-specific CD4 T-cells functioned any differently before or after administering the Ad5 vector. They found no significant difference in activation or expansion of CD4 T-cells in either the high- or the low-Ad5 antibody groups.
"It doesn't appear that vaccination increases the pool of potentially infectable CD4 T-cells in people with pre-existing immunity to Ad5," Ertl says. "When you look at the data together, they suggest we must look elsewhere to explain the link between previous Ad5 immunity and increased acquisition of HIV infection."
|Contact: Susan I. Finkelstein|
The Wistar Institute