Courtesy / Texas Biomedical Research Institute
On World AIDS Day, Dec. 1, we were reminded that 36.9 million people are living with HIV worldwide and 2.6 million of those are children under 15 years old. Once a death sentence, improved treatments over the past 30 years have made HIV infection mostly a chronic disease in higher income countries. Still, in 2014, 1.2 million people died of AIDS, 150,000 of them children.
In the early 1980s, Texas Biomed Research Institute’s Dr. Ruth Ruprecht was a medical resident at UCLA Medical Center, where she saw patients with unusual cancers brought on by immune deficiency. Clinicians called this “GRID,” Gay-related immune deficiency, and it had no known cause. In time, Human Immunodeficiency Virus (HIV) was identified as the cause and the disease, reaching beyond the young gay men where it was first identified, was called AIDS. Since then, Dr. Ruprecht has become one of the world’s leading experts in HIV research, motivated by the faces of those patients whose suffering touched her deeply.
Thanks to a $5 million grant from the National Institutes of Health awarded to Ruprecht and her collaborators at UCLA, the Food and Drug Administration and University of Pennsylvania, the promise of a post-exposure vaccine is on the horizon.
Most children with HIV are infected as infants when the virus is passed in utero from their infected mother, which is called perinatal transmission. In 1987, Dr. Ruprecht’s research showed that when AZT was given to an HIV-1 infected mother during the last trimester of pregnancy, the infant did not become infected with HIV most of the time. Since then, the standard of care has been to give highly active Anti-retroviral Therapy (HAART) to HIV-infected mothers late in pregnancy, dramatically reducing the number of infected babies, from as high as 45% without treatment to 5% with treatment.
However, this requires that the pregnant mother have access to prenatal care where she will be tested for HIV. The U.S. has recorded a 90% decline in the number of HIV-infected babies due to early diagnosis and treatment during pregnancy. Across the world, 67% of infected pregnant women received HAART in 2013, but that leaves another 33% with potentially infected babies.
In low- and middle-income countries, the World Health Organization (WHO) reports that the percent of pregnant women receiving HIV testing and counseling varies from 64% in Latin America to 25% in Southeast Asia. The result is that many more babies are born infected with HIV. The challenge then, is to find an effective treatment that will reduce infection or prevent progression to AIDS when the mother hasn’t had prenatal treatment.
In 2010, a woman with no prenatal care gave birth to a baby in a Mississippi hospital. During labor, it was determined she was HIV positive. The baby was given a high dose of anti-retroviral therapy at 30 hours old. For the next 18 months, as therapy continued, the HIV infection remained below the level of detection. Then the child was lost to follow up until 23 months, at which point the HIV infection was still below detectable levels despite five months without therapy. Believing the child cured, therapy was not restarted, and for 27 months, the HIV infection was not detectable.
The hope then, was that intense HAART after birth could also cure an HIV-infected infant. Unfortunately, in 2014, the child tested positive for HIV again, and it became clear that HAART alone was not sufficient when given after birth. There was just enough of the virus hiding in the child’s body to become reactivated. Continued treatment with HAART is necessary to prevent HIV re-activation in children infected during in utero.
A lifetime of medications is challenging and expensive, and pre-natal treatment is not always possible. The goal, then, is to create a vaccine that can be administered after birth to prevent the virus from becoming reactivated when HAART is stopped, creating a “functional cure.”
Vaccines tell the body’s immune system to respond immediately because it has seen the virus before. “It’s a combination of surveillance, patrol, and killing the offending virus before it has time to cause damage, “ explained Dr. Ruprecht. When we’re vaccinated for most diseases, we’re protecting ourselves from infection from an outside source. In the case of perinatal HIV, the infection is already in the child’s body.
Dr. Ira Berkower at the USFDA has developed a vaccine that induces strong killer cell activity. Killer cells “patrol the body and take out HIV infected cells that may become reactivated after HAART is stopped,” according to Dr. Ruprecht. With continual “patrols,” the vaccine will remove the HIV-infected cells before they can cause damage. The vaccine has been engineered to include components of simian human immunodeficiency virus (SHIV), a virus that contains parts of HIV and SIV.
With the recent NIH grant, Ruprecht and her team will treat infected infant rhesus monkeys with HAART, suppressing the virus. Once the virus is below detectable levels, they will give the vaccine to the animals. If the virus reactivates, the vaccinated animals should mount an immune response to it, preventing the increase in virus in the body.
A key factor in developing a vaccine is the safety of the vaccine vector. What better vector than a vaccine that’s already been “tested” in millions? Rubella vaccine has been used in the US since 1969. We have years of data to indicate it is safe and effective. So Dr. Berkower’s team developed the HIV vaccine using the rubella vaccine as a vector to introduce the HIV target antigens. If this vaccine can eliminate HIV infection or prevent re-activation of a perinatal infection, we already know the vaccine is safe in humans.
Dr. Ruprecht’s work has focused on maternal-child transmission of HIV infection, but it’s important to note that an adult’s immune system is more developed than an infant’s. It’s highly likely that a vaccine that generates a substantial immune response in infants would do the same or more in an adult.
“We are excited to launch this study and develop an attack plan against HIV that could both cure and provide a solid defense against further infection,” said Ruprecht.
The research by Dr. Ruprecht and her collaborators is yet another example of the world class scientific study happening in San Antonio.
These studies provide great hope for those living with HIV. Most important, though, is prevention and testing as the awareness movement’s motto states: “Know your status.”
For testing and counseling resources in San Antonio:
*Top image: Dr. Ruth Ruprecht, M.D., Ph.D., is director of the AIDS Research Program in the Department of Virology and Immunology at the Texas Biomed Research Institute, a world leader in independent biomedical research dedicated to advancing human health across the globe. Photo courtesy of Texas Biomed Research Institute.