March 19, 2001
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 journals 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 systems 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
Dr. Robinsons 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
The vaccines 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 bodys ability to recognize and react to
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 vaccines long-term protectiona critical measure
of vaccine success.
Another significant advantage of this vaccine is its simple inoculation
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
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
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