Faced with a shortage of critical reagents, Harriet Robinson of Emory University in Atlanta was forced to redesign an AIDS vaccine experiment. From that minor setback has emerged an impressive finding about the power of her vaccine approach. In a paper that will be published online on 9 March by Science, Robinson and her colleagues describe a two-step AIDS vaccine that appears to have stimulated long-lasting immunity.
Robinson and her colleagues at Emory and the National Institute of Allergy and Infectious Diseases (NIAID) designed their experiment around SHIV, a laboratory-made hybrid virus that's part HIV and part SIV, a simian AIDS virus. They first injected 24 monkeys with a vaccine that contained several SHIV genes stitched into bacterial DNA. Later, the animals got a booster shot consisting of a variety pack of SHIV genes carried by recombinant modified vaccinia Ankara (MVA), a version of the virus used as the smallpox vaccine. Rather than preventing infection, both the naked DNA and MVA vaccines primarily stimulate the immune system to eliminate already infected cells.
Robinson and colleagues planned to test this approach by "challenging" the vaccinated monkeys with an inoculum of SHIV placed into the animals' rectums. To do this, they needed a "challenge stock," a batch of SHIV that had been tested on monkeys to determine the minimum amount of virus needed to establish an infection rectally. After she had started vaccinating monkeys, Robinson realized that she would have to make the challenge stock herself, which took three tries.
By the time they challenged the vaccinated monkeys, 7 months had elapsed since the animals had received a booster shot. "Originally we had planned to challenge at 3 months," laughs Robinson. The 24 vaccinated animals became infected with the SHIV, but 20 weeks later, 23 had controlled the infection and had suffered no immune damage. The four unvaccinated control animals, in contrast, all had consistently high levels of SHIV in their blood, and they subsequently died from AIDS.
"This is the closest thing to a real-life challenge that we've seen yet," says James Bradac, who heads the NIAID division that oversees monkey trials of AIDS vaccines. An HIV version of this DNA/MVA vaccine is slated to begin human trials in the United States by early next year.