VRC researchers take
big step toward AIDS vaccine

By Lillian Kim

Researchers at Yerkes’ Vaccine Research Center (VRC) have developed a multiprotein AIDS vaccine that has prevented the development of AIDS in monkeys infected with a highly virulent HIV analogue seven months after vaccination. The study results are reported in the March 9 online version of Science and will be published in the journal’s print version later this month.

The federally funded study indicates that the vaccine, composed of two DNA priming vaccines followed by a modified poxvirus booster, successfully primes the immune system’s “memory” and provokes a strong immune response. This relatively simple vaccine regimen has achieved better protection than any other HIV vaccine candidate to date, placing the vaccine among the most promising candidates moving toward human clinical trials.

“We have been really excited about the level of control we have achieved with our memory response,” said lead author Harriet Robinson, chief of microbiology and immunology at Yerkes and a VRC faculty member. “Even among the groups that received the low-dose vaccine, the infections were controlled.”

“Dr. Robinson’s exciting results represent a major turning point in our quest for an AIDS vaccine,” said VRC Director Rafi Ahmed. “Using the best animal model available, [she] has provided proof that a vaccine can prevent the development of AIDS. The next step, and the most important one, is to determine how effective this vaccine is in humans. This is now the highest priority of the Emory Vaccine Research Center.”

The vaccine’s greatest strengths are its abilities to cause expression of multiple proteins and to provide memory immune responses months after inoculation. Unlike other candidates, this vaccine causes expression of the three major polyproteins (Gag, Pol and Env) expressed by HIV. This induces immune responses to all three proteins instead of only one or two, thus increasing the body’s ability to recognize and react to HIV.

“We think the expression of multiple proteins was critical to the success of our vaccine,” Robinson said.

Also, the researchers waited seven months after the last inoculation to test the vaccine’s long-term protection—a critical measure of vaccine success.

Another significant advantage of this vaccine is its simple inoculation regimen.

Previous studies of HIV vaccine candidates have involved as many as six inoculations, while this vaccine required only three. “Because this is a relatively simple vaccine, it is more consistent with actual human use,” Robinson said.

In the two-year study, Robinson and her research team vaccinated a total of 24 monkeys with a series of three inoculations: two DNA-based vaccines delivered eight weeks apart to prime the immune system, and a single booster administered at 24 weeks. The monkeys were categorized in four groups by vaccine dosage (high versus low) and inoculation method (just under the skin versus deep in the muscle). Researchers compared the 24 vaccinated monkeys to a control group including two mock immunized monkeys and two non-vaccinated animals.

Seven months following the booster, the monkeys were infected with a highly virulent hybrid of simian and human immunodeficiency viruses. After infection, the non-vaccinated monkeys rapidly developed high levels of virus, 100 times that typically found in HIV-infected humans, and progressed to AIDS. By contrast, the vaccinated animals maintained low levels of virus characteristic of people who are infected with HIV but do not develop AIDS over very long periods of time. Similarly, the vaccinated monkeys remained healthy.

It is important to note that the vaccine did not prevent infection in the vaccinated monkeys. Instead, the vaccine controlled infection by keeping the virus from replicating in large numbers. Maintaining a chronic, low-level infection prevents progression to AIDS and reduces the risk of virus transmission, since higher viral loads are associated with greater infectiousness.

The HIV version of this vaccine will move into clinical trials in humans in 2002.