Deciphering Immunology’s Dirty Secret

Before Bali Pulendran started his first major protocol at the Emory Vaccine Center in Atlanta, he wanted to meet his subjects. So, in the fall of 2004 he and postdoc Marcin Kwissa drove the 25 miles to Lawrenceville, Georgia, and the Yerkes Primate Research Center’s field station. There, Pulendran and Kwissa stood face to face with their trial participants: 25 rhesus macaques. “I remember staring at them and thinking: ‘Wow, these are who we’re going to be vaccinating’,” says Pulendran.

Nearly two years have passed and those monkeys now reside in the next building over from Pulendran’s office, where they’ve entered the final phases of a clinical trial for an HIV DNA vaccine developed at the center. The vaccine has already successfully reduced viral load in nonhuman primates, and it’s being tested in humans. Pulendran is adding a new twist, however. Two groups of the immunized monkeys have also received an adjuvant that targets toll-like receptors (TLRs), key components of the innate immune system.

HIV vaccine strategies have been vexed by, among other things, the virus’s ability to disarm the immune system and the immune system’s inability to generate antibodies against the virus. But discoveries just in the past decade have uncovered a wellspring of innate immune targets that appear to converse with the adaptive response and may aid in shutting down HIV. “By giving a TLR ligand with the DNA vaccine, can you make the immune response stronger and get an even more profound effect on the viral load?” he asks. The strategy is young, and at 40 years old, so is Pulendran.

In August 2006, the 25 monkeys were brought to the Atlanta campus to be infected with SIV, and the excitement is palpable. The true test will be whether the subjects that received TLR adjuvants have significantly reduced viral loads. Pulendran has been awaiting the results from the virology lab for weeks. “I’m hopeful,” he says, pausing and then drawing in a deep breath. “But we’ll see.”

Read the entire story, Deciphering Immunology’s Dirty Secret, in The Scientist.