Jun 272012

The aging fisherman in Ernest Hemingway’s novel “The Old Man and the Sea” swilled shark liver oil to ward off colds and flu. Now Novartis AG is betting it can help protect against AIDS.

Novartis is teaming up with Sanofi, adding a boosting agent to the French drugmaker’s earlier attempt at making an AIDS vaccine. That first effort lost its punch over time. The new combination represents the most advanced attempt to develop an effective shot against the deadly pathogen. Human tests are scheduled to start next year or early in 2014.

HIV infection, which causes AIDS, was once a death sentence. Today the disease can be blunted with drugs but only a vaccine can deliver a knock-out blow. If the Novartis-Sanofi project pays off, it will be the world’s first effective vaccine against AIDS, which has killed 30 million people over 30 years.

“It’s got a good chance of success,” said Nelson Michael, director of the U.S. Military HIV Research Program, which is also participating in the project. “We’re going to need a vaccine to wipe this thing off the planet.”

Developing a vaccine against AIDS, which infects a new person every 12 seconds, is one of the biggest challenges facing the medical research community. The subject will be discussed at an AIDS conference in Washington next month and serve as the focus of another gathering in Boston in September.

HIV has proved a wily foe, constantly mutating to defeat virus-fighting drugs. Because vaccines work by training the immune system to recognize a pathogen, researchers have struggled against an ever-changing target.

Staying Power

Previous attempts by Sanofi, VaxGen Inc. and Merck & Co. with single vaccines have all ended in failure. Now Sanofi and Novartis are seeking to defeat HIV with a two-pronged approach to marshal the body’s defenses against the virus.

There are a handful of experimental shots currently being tested to protect against HIV. The one that combines Sanofi’s ALVAC with the Novartis shark liver oil booster known as MF59 is the furthest along, said Nina Russell, deputy director of HIV at the Bill & Melinda Gates Foundation, which is providing funding.

“The next generation products, even if all goes well, are significantly behind,” she said in a telephone interview. “This certainly affords us the opportunity, if we can get to a sufficient level of efficacy, to have a significant impact on the epidemic.”

Gene Smuggling

Sanofi’s ALVAC stunned researchers in 2009 when, used with another vaccine from VaxGen in a test of 16,000 volunteers in Thailand, it reduced HIV infections by 31 percent over three years. Its efficacy reached 60 percent after the first year, then waned. Novartis is hoping its booster, already used to stimulate immunity in its Fluad seasonal influenza vaccine, will give ALVAC more staying power.

“We need to make sure that we maintain the immunity longer, and I think MF59 is going to do that,” said Rino Rappuoli, who heads vaccine research at Basel, Switzerland-based Novartis.

ALVAC uses a canary pox virus that’s been disabled so it doesn’t sicken humans to smuggle three HIV genes into the body. That fools the immune system into thinking it’s under attack from HIV, prompting it to pump out defensive T-cells that are then primed to ward off the virus in case of a genuine attack.

The Thai study results prompted Paris-based Sanofi to seek a partner “with industrial muscle” to continue investigating ALVAC’s potential after VaxGen had given its rights to a non- profit organization, said Jim Tartaglia, vice president of research and development for new vaccines at the company.

“Novartis quickly came to mind,” Tartaglia, who is also one of the inventors of ALVAC, said in a telephone interview from Swiftwater, Pennsylvania.

Rivals Work Together

Novartis and Sanofi, which compete in selling vaccines against flu and meningococcal disease, are trying to improve on the results of the Thai test in groups at high risk of infection.

One clinical trial will test the product in gay and bisexual men in Thailand, and the other in heterosexuals in South Africa, which has more people with HIV than any other nation. The results probably won’t be available until 2019, said Elizabeth Adams, the chief medical officer at the U.S. National Institute of Allergy and Infectious Diseases’ AIDS division.

Adams co-chairs the group planning the tests, which includes her agency, the Gates Foundation, the U.S. military, the Seattle-based HIV Vaccine Trials Network, Sanofi and Novartis in a coalition dubbed the Pox-Protein Public Private Partnership, or P5. The NIAID and Gates are funding the project.

‘Good for the Eyes’

While participants in the Thai trial received six shots over six months, those in the South African study will get as many as eight injections over a year in an effort to make the protection more durable, according to Adams.

Novartis acquired the MF59 booster from Chiron Corp., which it bought for $5.3 billion in 2006. Chiron developed the milky liquid based on squalene, a chemical produced by the human liver and extracted for commercial use from shark liver oil, with an HIV vaccine in mind in the 1990s, before research setbacks in the field caused it to shift the product to flu, according to Rappuoli.

People on the coasts of Norway and Sweden have used shark liver oil for centuries to help heal wounds and treat respiratory and digestive illnesses, according to the American Cancer Society. In Hemingway’s book, which describes the struggle of a fisherman with a giant marlin, the protagonist drinks a cup of the oil each day because it’s “very good against all colds and grippes” and is “good for the eyes.”

Arsenal of Weapons

Novartis uses the squalene extracted from shark livers to make MF59, Rappuoli said. He’s quick to add that about 95 percent of the compound harvested from the fish is used for cosmetics. Scientists are working on ways to derive the compound from olive oil, he said.

In the vaccine, MF59 will be injected with an HIV protein known as gp120 that HIV uses to gain entry to cells. That will prompt the immune system to pump out antibodies. The combination is being developed in the company’s labs and will be ready at the end of next year, when trials with ALVAC are scheduled to begin, according to Rappuoli.

The vaccine is being designed against the strain that predominates in southern Africa, the region with the highest prevalence of infections. It may not work as well against those that circulate in the U.S. and Europe, says Sanofi’s Tartaglia.

Though a shot may not be approved until 2022, according to NIAID’s Adams, an expanding arsenal of weapons including testing, condoms, anti-AIDS drugs, male circumcision and education are helping to drive down infections and deaths. Those tools will continue to be important even with a vaccine, the U.S. military’s Michael said.

“To kill this dragon is going to take more than one knight,” says Michael, who as director of the military’s HIV research program ran the decisive ALVAC test in Thailand. “A vaccine isn’t a panacea. But in the absence of one, the epidemic will soldier on.”

Simeon Bennet