1. Africa's victory, Africa's sorrow

2. A tough challenge

3.Multiple proteins

4. Immune-system helper

5. Making sense of vaccines

Rhesus macaques are a favorite animal for testing AIDS vaccines, because they get a related disease caused by the simian immunodeficiency virus (SIV).
Photo by Robert Dodsworth. Courtesy Wisconsin Regional Primate Research Center

By 1993 the repeated failure of any candidate vaccine to prevent infection caused scientists to set lower sights. Could vaccines stimulate antibodies or other defense mechanisms to reduce or prevent disease rather than prevent infection?

In April, researchers at the Yerkes Regional Primate Research Center at Emory University announced that a vaccine regimen had prevented immunodeficiency disease in 24 monkeys (see "Control of Mucosal... " in the bibliography).

The vaccinated monkeys got infected, but they did not get AIDS. Only one of the 24 monkeys showed "some loss of control of the virus," says Harriet Robinson, the Yerkes chief of microbiology and immunology, who directed the test.

Robinson's group immunized 24 rhesus macaque monkeys with two doses of DNA -- in essence, two separate vaccines -- that coded for the three major viral proteins. The viral DNA came from primate and human strains of the immunodeficiency virus.

The third shot contained an unrelated virus that enhanced the immune reaction.

Seven months later, the monkeys were infected with a virus that the researchers described as "highly pathogenic." To simulate the sexual transmission that commonly spreads AIDS, the virus was introduced into the rectum.

Seven-month solution
Every monkey -- including the four unvaccinated controls -- got infected. But only the controls got sick. "We have been really excited about the level of control we have achieved with our memory response," says Robinson. She notes that the vaccine strategy primed the body to recognize all three major HIV proteins, thus improving the ability to respond to the virus.

The study was promising, but no panacea. The vaccine required three injections -- a problem in the developing world, where an oral vaccine, especially one that needed no refrigeration, would be preferable.

Some of these boys, in a photo taken in 1980 in the village of Kabundu, Senegal, may already have AIDS.
© David Tenenbaum

Perhaps more important, the "challenge" virus -- which tested whether the vaccine worked -- was similar to the virus used to make the vaccine. That raises the question of whether the vaccine would protect against other HIV strains. "In the real world," observes Jon Cohen, a correspondent for Science magazine, "you are likely to be confronted with a virus that doesn't look a great deal like the vaccine virus, but it's reasonable to start with an experiment that's tilted to succeed."

However, Robinson says the vaccine strain did not create antibodies against the challenge strain. "Thus, the control of the infection occurred in the absence of neutralizing antibody," as a real-world vaccine would need to do.

The lower standard of protection conferred by vaccines that simply control the virus also raises ethical concerns. Since most people assume getting a "shot" makes them immune to a disease, would people who don't have AIDS get the vaccine and abandon safe-sex practices? Would AIDS patients get the shot and do likewise?

It's too soon to know, but the AIDS Vaccine Evaluation Group in the National Institute of Allergy and Infectious Diseases, plans to move ahead with a human trial of the multiple-injection vaccine in 2002. Ethicists will be involved, Robinson says, "to try to handle ethical issues correctly." More on the research.

If the immune system worked, AIDS wouldn't matter.