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San Antonio scientists create breakthrough in HIV research
August 8, 2018

Dr. Ruth Ruprecht said the antibody that she and her researchers worked with had been mostly ignored for use in fighting HIV. Jerry Lara / Staff photographer

By Chase Karacostas, Staff Writer, San Antonio Express-News

San Antonio researchers have made a breakthrough in the fight against AIDS, which could lead to the development of a topical gel to protect against the disease.

In a peer-reviewed study involving rhesus monkeys, Dr. Ruth Ruprecht and her team at the Texas Biomedical Research Institute showed that a previously unstudied class of antibodies is effective in protecting against simian-human immunodeficiency virus.

“It’s an important step forward,” said Dr. Philip Keiser, director of the International HIV Program and Clinic at the University of Texas Medical Branch at Galveston. Keiser was not involved in the study.

“Back in 1985 when the virus was first discovered, we all naively thought that you could just grind up the virus and inject it into people and that would act as a vaccine,” he said. “And, unfortunately, over 30 years that hasn’t been the case.”

Ruprecht’s team is now working on creating other kinds of antibodies to increase effectiveness of the gel. In several years, the team will turn its focus to re-creating similar antibodies in humans to determine whether the gel works as well against HIV as it did against the simian HIV.

“There has been tremendous progress, but the war is not over,” Ruprecht said.

To date, there has been one major development in protecting against the virus, but it is expensive and cumbersome to take.

Pre-exposure prophylaxis, known as PrEP, reduces the risk of HIV transmission through sex by more than 90 percent. But it must be taken every day for a full week before becoming effective for anal sex and 20 days for vaginal sex. That cycle must also be restarted if more than a few doses are missed, according to the Kind Clinic, a medical center in Central Texas that provides PrEP for free or at a low cost.

Ruprecht’s team put the antibodies in a topical gel that is applied to vaginal or anal areas. It focuses on transmission through those mucosal sites, which is how about 90 percent of all infections occur worldwide. It would be much easier to use than PrEP.

The researchers used six rhesus macaques, a type of primate with a similar immune system to humans, in their study. The gel, which contained IgM, or Immunoglobulin M, antibodies created by the team, protected four of the six primates from infection with SHIV. The gel was effective in preventing infection within 30 minutes of application.

The three-month study, conducted by the institute, UT Health San Antonio and the University of Virginia, was published in the July edition of AIDS, a peer-reviewed journal.

The discovery by Ruprecht’s team, Keiser and others say, provides new hope not just for immediate protection but for an actual long-lasting vaccine in the future.

“If we can get to a point before I retire where we are vaccinating everybody and knowing we can potentially wipe this virus off the face of the Earth, I think that would be a wonderful thing,” said Keiser, who has been working on HIV research for more than 30 years.

Creating an antibody

The IgM antibody Ruprecht’s team created isn’t a vaccine itself. The antibodies fight off HIV for a short period, but a vaccine teaches the human body how to produce the antibodies to provide long-term protection. The team’s research could lead to the development of a vaccine.

In the meantime, the gel could provide another option for prevention, not just treatment. It would not only protect during sex, but would prevent an HIV-positive mother from transmitting the disease during childbirth.

“HIV is such a tricky and treacherous enemy, that you need to have as many defenders as you possibly can,” Ruprecht said.

Today, nearly 37 million people around the world live with HIV, the human immunodeficiency virus that causes AIDS, according to the World Health Organization.

HIV attacks the immune system and suppresses it to a level that makes people more susceptible to “opportunistic infections,” illnesses such as pneumonia that are usually survivable but can easily become deadly to a person with a weakened immune system.

There is no cure for HIV.

Research for preventive medicines has focused on Immunoglobulin G, which is good at attacking HIV but has only two possible areas where it can attach to the virus.

Ruprecht’s team had the idea of transplanting genes from Immunoglobulin G into Immunoglobulin M, which is not as good at binding with HIV but has 10 possible areas where the virus can be captured.

In creating the enhanced IgM, the researchers got “the best of both worlds”: an antibody with 10 binding sites that are all excellent at attacking HIV, explained Eileen Lafer, a professor of biochemistry at UT Health who worked with Ruprecht on the study.

“That’s a really novel approach because (Ruprecht) documented that this actually has protective effects against HIV, or in this case, SHIV,” Lafer said. “It’s really setting the stage for potentially a whole new group of therapeutics that could be developed against HIV.”

Ruprecht said the IgM antibody had been mostly ignored for use in fighting HIV because it is the first immune system response. Scientists believed that IgM would not stick around long enough to fight off HIV once other antibodies showed up, but in her research, Ruprecht proved otherwise.

“We showed that this was a potent way of preventing virus transmission,” Ruprecht said.

The study was supported by a Southwest National Primate Research Center grant from the National Institutes of Health.

Holy grail

While diseases such as smallpox have been almost completely eradicated, Ruprecht said HIV has been difficult to beat because of how quickly it changes. Unlike most organisms, there is no method to ensure accurate copying of genetic material every time the virus duplicates.

“There isn’t just an HIV. There are myriads of different strains. Even an infected person has millions of different (strains),” Ruprecht said. “It’s, in military terms, like the problem of shooting at a moving target.”

In the 30 years since Ruprecht began studying HIV, significant progress has been made in treating the disease. In the 1990s, she was involved in the development of AZT, the first successful treatment for HIV. Such antiretroviral therapies have transformed an HIV diagnosis from a death sentence into a chronic, but survivable, illness.

Still, the holy grail is a vaccine.

Keiser recalled that when he started studying HIV in the 1980s, he would often go home to find his patients’ obituaries in the Sunday edition of the Dallas Morning News.

“When I first started treating HIV, we treated a bunch of young men, and they all died,” Keiser said, noting that, while that doesn’t happen any longer, the virus is still a serious problem.

“We may or may not get a cure, but our best chance at eliminating this infection, since it’s only in human beings, is through a vaccine.”

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