At #8 is the work of Dave Morgan of the University of South Florida and his colleagues, showing that a vaccine against the amyloid-beta peptide that is so characteristic of Alzheimer’s sufferers prevents memory loss in a mouse model of the disease. An earlier paper (D. Schenk, et al., Nature, 400[6740]: 173-7, 1999) proved that vaccination reduced the formation of amyloid-beta plaques, but offered no clues as to its effect on behavior. Morgan, and another (strangely less-cited) paper from Peter St. George-Hyslop’s group at the University of Toronto [C. Janus, et al., Nature, 408[6815]: 979-982, 2000), showed that in addition to preventing the formation of plaques, vaccination also prevented memory loss.

Both groups tested the ability of mice to swim to a platform hidden just beneath the surface of the water. As they cannot see the platform, the mice have to remember where it is from trial to trial. Morgan’s group left the platform in the same place for each trial on a given day, but moved it randomly from day to day. The mice therefore had to use their short-term memory to find the platform. St. George-Hyslop’s group left the platform in the same place for five consecutive days, challenging long-term memory, and also tested the mice roughly once a month for three months, thus tracking changes over time. In both, vaccinated mice performed better than unvaccinated controls. "This is big news," said Paul Chapman, who studies Alzheimer's at Cardiff University in U.K.

So is the demonstration, at #13, by Harriet Robinson of Emory University in Atlanta, Georgia, and colleagues that a combination of two different kinds of vaccine enables rhesus monkeys to resist infection with an AIDS virus (R.R. Amara, et al., Science, 292[5514]: 69-74, 2001; with 32 citations this period). The big problem with vaccines against HIV is that the virus mutates so rapidly. It is thus likely to differ from any previous protective vaccine. Robinson tripled the odds of the virus mutating away from the vaccine by incorporating three different antigens into the vaccine. And she gave it in two forms. First, naked DNA containing genes for the three antigens. This is taken up by cells and boosts the production of T killer cells primed to tackle cells infected with HIV. A few weeks later the monkeys received a pox virus (similar to the one used to help eradicate smallpox) engineered to contain the same three antigen genes. The modified pox virus infects cells and triggers antibody-mediated immunity.

This regime enabled monkeys to successfully resist a challenge with a virulent AIDS virus, which killed their unprotected colleagues within months, for more than a year. The monkeys were indeed infected, but managed to keep the amount of virus below detectable levels. "That has tremendous implications for extending life expectancy and also for transmission," Robinson said. "If you take the viral load way down, you really are going to reduce transmission."

AIDS and Alzheimer’s are, of course, very different diseases. But for both, vaccination has long seemed both an ideal solution and a mirage. For HIV/AIDS the beauty of a vaccine, especially one based on DNA and engineered pox virus, is that it is likely to be much more affordable than existing drug treatments. Approaches very similar to Robinson’s have been through trials in the U.K. and in Kenya, with promising results. Andrew McMichael, of Oxford University in the U.K., designed a vaccine around the T killer cells found in the blood of those few Kenyan prostitutes who seemed to have a natural immunity to HIV/AIDS. The results, he says, are encouraging, but he cautions that there is still a long way to go.

The Alzheimer’s vaccine, by contrast, leapt to prominence when Elan, a drug company, reported promising early results but is now bogged down in controversy. Elan abandoned Phase II trials when it became clear that the vaccine was somehow causing inflamation in the brain, with symptoms similar to encephalitis or meningitis. In November 2002, studies showed that in mice the vaccine caused bleeding in the brain (M. Pfeifer, et al., Science, 298: 1379, 2002). Morgan thinks that bleeding may actually be a second side effect, to put alongside the inflamation. "Before we put any more vaccines in people, we need to know what the problem was," he said. Scientists trying to do just that may be responsible for the uptick in citations.