Slowing down immune system may improve HIV vaccines

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Schematic representation of the key structural features of SIV and HIV-1 entry into T cells.

Like a skittish driver slamming on the brakes, a special class of T cells may be limiting the effectiveness of therapeutic vaccines for HIV by slowing the immune system response too soon, University of Pittsburgh health science researchers reported in a recent issue of PLoS ONE. Their study, the first to look at the role of regulatory T cells in therapeuticHIV vaccines, may help researchers improve the efficacy of such vaccines by devising methods to circumvent the braking mechanism of these cells.

Regulatory T cells (Treg) are critical because they suppress the immune response, preventing the immune system from turning against itself. Without the braking action of Treg, autoimmune disease could flourish. But what if these cells are shutting down the immune response before a therapeutic vaccine has had a chance to bolster immunity against HIV?

When we removed Treg from blood cells, we found a much stronger immune response to the vaccine, giving us insight into how we can develop more effective HIV vaccines.

—Charles R. Rinaldo Jr., PhD, University of Pittsburgh

Pitt researchers sought to answer this question as follow-up to a clinical trial of a therapeutic dendritic cell-based HIV vaccine they developed to activate the CD8, or killer T cell, response. First reported in 2008, their findings indicated only limited success of the vaccine in the 17 patients enrolled in the trial. For the current study, the researchers went back to the freezer, removed Treg from the patients’ blood cell samples, and found it was masking a two-fold increase in immune response to HIV induced by the vaccine.

“When we removed Treg from blood cells, we found a much stronger immune response to the vaccine, giving us insight into how we can develop more effective HIV vaccines,” said Charles R. Rinaldo Jr., PhD, professor and chairman of the department of infectious diseases and microbiology at Pitt’sGraduate School of PublicHealth.

“Treg normally shuts down CD8 responses once the infection has been controlled, but in this case it appears to be putting on the brakes early and possibly limiting the vaccine’s ability to do its job effectively,” said Dr. Rinaldo, the study’s lead author, in a statement.One theory is thatHIV infection drives up Treg, which in turn shuts down the HIV-1- specific CD8 T cell response, he said.