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Science – HIV Vaccine Success May Take Decade to Unravel Why It Works

Tom Randall

Sept. 28 (Bloomberg) — The surprise finding that a combination of two experimental vaccines reduced HIV infections is confounding long-held assumptions about the AIDS virus and sending scientists back to the laboratory to address mysteries that may take a decade to solve.

A study of 16,000 volunteers in Thailand, reported last week, found those getting the immunization had a 31 percent lower infection rate than those given a placebo, the first time any vaccine had positive results. The report startled scientists, many of whom had dismissed the trial as a dead end, said Anthony Fauci, director of the National Institute of Allergy and Infectious Disease in Bethesda, Maryland.

The injection must be at least 50 percent effective before widespread immunization is feasible, said Josh Ruxin, director of the Access Project program in Rwanda. Researchers led by Fauci say they can’t improve the vaccine until they understand how it blocked infections, or why it failed to show any benefit for people who still got infected with HIV.

“Some of our preconceived notions about what to measure and what we think is important might have just been turned on its head,” said Colonel Nelson L. Michael, director of the division of retrovirology at the Walter Reed military hospital in Washington, in a news conference. The U.S. military helped conduct the trial.

HIV infects about 7,400 new people every day worldwide, and led to 2 million deaths in 2007 according to UNAIDS. While there are treatments that can suppress the virus for those who can afford them, there is no cure. Even after the success of the vaccine study, a much-needed vaccine may yet be 10 years away, according to the Access Project’s Ruxin and Jeffrey Kraws, chief executive officer of Crystal Research Associates in New York.

Two Vaccines

The Thai study combined two vaccines, neither proven. One was ALVAC, developed by Sanofi-Aventis SA in Paris. The other was AIDSVAX, created by a Genentech Inc. spinoff, VaxGen Inc. AIDSVAX was later licensed to Global Solutions for Infectious Diseases, a nonprofit group led by Donald Francis, who left VaxGen in 2003 after initial trials failed.

AIDSVAX, which failed in previous tests, contains an HIV protein called gp120 that’s designed to encourage the body to produce neutralizing antibodies to recognize and destroy HIV before it can infect healthy cells. ALVAC focuses on increasing cellular responses to attack the virus. The theory behind the combination was that ALVAC would “prime” the immune system to respond, and AIDSVAX would “boost” the antibody response.

Measurable Signs

The unexpected success “tells us that we don’t even know what the correlates of immunity are,” Fauci said, referring to the measurable signs that a person has developed defenses against a virus. “But it does give us now a bit more direction for trying to track down what it is this vaccine did that led to this modest degree of protection.”

Antibodies, protective proteins developed in the body in response to a virus or vaccine, are the most common signal of immunity. Researchers haven’t identified neutralizing antibodies produced by the experimental vaccine, and previous quests to induce such antibodies have ended in failure, Fauci said. Scientists are also searching for signs of boosted cellular defenses that might be key to the vaccine’s success.

“We’re not even close to being finished,” Fauci said.

Scientists also don’t understand why the combination vaccine failed to show benefit for people who still got infected with HIV. Other vaccines that aren’t 100 percent effective, such as the seasonal flu shot, typically make symptoms less severe in patients who still get sick.

Virus Levels

In the Thai trial, vaccinated patients who still contracted HIV had the same levels of virus in their blood as patients who never received the vaccine. That was perplexing, as researchers assumed it would be easier to reduce the so-called viral load than to prevent infection, said Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition in New York.

Collaborators on the Thai study are continuing to track the vaccinated patients who were infected in a study called RV152 to see whether the virus levels diverge and whether symptoms are lessened. There are limited supplies of the shots, though, and it will take time to produce enough for more tests, said Donald Francis, of Global Solutions for Infectious Diseases, at the news conference announcing the finding last week.

“The samples and specimens collected from this trial have become a precious resource,” Warren said in a telephone interview. “Over the next few months we’ll see some consensus as to what are the elements of trials that need to be conducted with the current samples.”

No Natural Immunity

After people are infected with HIV, treatment with antiviral drugs can keep HIV at bay for years, allowing patients to have healthy and productive lives, said Michel Kazatchkine, executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. However, the virus can’t be driven from the body, so patients can’t develop natural immunity for doctors to use as a model for vaccine research.

“You start from nowhere,” Kazatchkine said in an interview. “Is it one of the components? Is it the mixture? Is it the way it was administered? We need to build more science, more pilot trials, and then one day, another big trial.”

“You’re looking at 5, 10 years minimum to have commercial viability here,” said Kraws, CEO of Crystal Research Associates. “There was a reason why this failed for Sanofi- Aventis the first time, and it is not because they are stupid. We have to analyze it further and see how it works and make adjustments.”

Retention Rate

The Thai study required six shots and 19 visits from patients over the course of three years, said Warren, of the AIDS Vaccine Advocacy Coalition. Of those who received the shots, 51 became infected with HIV, compared with 74 who received a placebo. The results wouldn’t have carried statistical weight without the study’s 90 percent retention of patients, an unusually high rate that will be difficult to replicate in future studies, Warren said.

“Since the early 1980s it has been an annual letdown, an annual cause for collective depression that every year we seem to be about 10 years away from an effective AIDS vaccine,” said Ruxin, whose Access Project helps Rwandan health facilities deliver care for people with AIDS.

“The next 10 years feel better than the last, but it still feels like it will be 10 years,” Ruxin said in a telephone interview from Kigali, Rwanda.

To contact the reporter on this story: Tom Randall in New York at


September 28, 2009 - Posted by | Uncategorized |

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