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When Phillip “Terry’’ Ragon, a wealthy Cambridge entrepreneur, agreed to accompany Dr. Bruce Walker to South Africa 12 years ago, Ragon tried to lower expectations. During the long flight, he told Walker, a prominent AIDS researcher at Massachusetts General Hospital, that there were so many worthwhile charities, chances were slim that he’d donate money to his cause.

All that changed after three days spent visiting doctors in the large coastal city of Durban as they treated patients dying from AIDS.

That 2007 trip led to an announcement this week that Ragon and his wife, Susan Ragon, are donating $200 million to Mass. General, the largest single gift in the hospital’s 208-year history. The gift, announced Thursday, will permanently endow a vaccine research center headed by Walker and created a decade ago by a $100 million gift from the Ragons.

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“We now have an institute that will be here forever,’’ Walker said.

Researchers affiliated with the Ragon Institute, a joint venture with Harvard University and the Massachusetts Institute of Technology, are now testing a potential HIV vaccine in South Africa. Since 2009, the center has expanded its goals to include developing vaccines for tuberculosis and influenza.

The $200 million gift is among the first large donations in Mass. General’s $3 billion fund-raising campaign, which began more than a year ago and is believed to be the largest fund-raising effort by a single hospital in the United States. The hospital intends to put the money toward a range of research, patient care, and education initiatives, including a planned $1 billion expansion.

Mass. General’s president, Dr. Peter Slavin, said the Ragons’ gifts have allowed scientists to be more flexible and creative and take more risks in pursuing projects. Most researchers must seek government grants, which involves delays and uncertainty. This allows the Ragon Institute “to come up with an idea one day and start working on it the next,’’ Slavin said.

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Terry Ragon is the sole owner of InterSystems, a Cambridge company he started in 1978 that sells database software to hospitals, banks, and other industries. He said his interest in international philanthropy was sparked during his senior year in high school in Bogota, where his father, a US Air Force fighter pilot, was stationed at the time.

“I saw such poverty,’’ Ragon said. “Kids would be on the street without a stitch of clothes.’’

After earning an undergraduate degree in physics from MIT and becoming a successful businessman, Ragon funded the building of a new school in Bogota and the expansion of another.

In 2017, he and his wife signed the Giving Pledge, the campaign by Bill and Melinda Gates and Warren Buffett to persuade the world’s wealthiest people to give much of their fortunes to philanthropy.

Ragon crossed paths with Walker almost by chance in 2007. Walker was conducting AIDS research at McCord Hospital in Durban, and Ragon’s company provided electronic medical records to the hospital. A salesman kept after Walker to meet Ragon.

When Walker returned to Boston, he made an appointment. When they eventually met, the two men exchanged business cards, and then Walker “blurts out ‘I have no idea why I am here,’ ’’ Ragon, 69, recalled. “I said, ‘I have no idea why you are here, either.’ ’’

Walker began telling him about his work, and that led to the suggestion that Ragon join him in South Africa several weeks later.

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Ragon spent the first day in a doctor’s office as she treated a succession of women with HIV infections. The third patient could barely breathe. The doctor asked her if she believed in Jesus and suggested it was time to make plans to meet him, he recalled.

“All the beds were full, so she was discharged back out onto the street. I have no idea what happened to her,’’ Ragon said.

A year later, the Ragons gave $100 million to start the institute, spread out over 10 years. The plan: Pursue science in a different way, by bringing together the best researchers from separate fields to solve problems. The unifying vision was to harness the immune system to prevent and treat diseases that have a global effect.

The Ragons have given more than $400 million total to Mass. General, including a previous $50 million toward a Ragon Institute endowment. Terry Ragon has been a member of the hospital’s board since 2014.

Dr. Dan Barouch, a founding member of the institute who is also affiliated with Beth Israel Deaconess Medical Center, and collaborators are now testing a novel HIV vaccine in South Africa in a clinical trial involving 2,600 women at risk for the virus. HIV destroys immune cells that fight infection and causes AIDS, which is the final stage of an HIV infection.

Several large vaccine trials have failed in recent decades because the “virus mutated more quickly than the vaccine could respond,’’ said Dr. Kenneth Mayer, medical research director at Fenway Health, a comprehensive health center in Boston.

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Still, Mayer believes the approach being tested now is particularly promising because it includes a “mosaic’’ regimen designed to go after different strains of the virus, which creates various subtypes around the world. He said the Ragon Institute is among the leaders in AIDS research in the United States, along with several other universities and the National Institutes of Health.

Researchers at the Ragon “are very flexible and very creative and they have been making a difference,’’ he said. “But the advancing of science is slow.’’


Liz Kowalczyk can be reached at kowalczyk@globe.com.