New HIV vaccine could expose latent virus and kill it

mediknit, healthcare, hiv
Antiretroviral therapy may soon be obsolete, as scientists have successfully used immune cells to kick the dormant form of HIV out of its hiding place and destroy it. The findings may soon lead to an HIV vaccine.

According to recent estimates, around 1.1 million people in the United States have HIV.

With the help of antiretroviral therapy, over half of these people now have a very low level of the virus.

This means that they can no longer trasmit it to other people.

Antiretroviral therapy can keep HIV in check so well that the virus is near-undetectable in the blood.

However, HIV continues to “live” in latent form, so people with it must keep taking the medications to prevent it from flaring up.

Antiretroviral therapy can have a host of side effects. These may include gastrointestinal problems, cardiovascular problems, insulin resistance, and bleeding events, as well as effects on bone density, liver health, and neurological and psychiatric health.

So, the search for an HIV cure is ongoing. Now, new research may have found a way to “drag” the virus out of its hiding place and neutralize it. The findings may lead to a vaccine that would allow people living with HIV to stop taking antiretroviral medication every day.

Senior study author Robbie Mailliard, Ph.D. — an assistant professor of infectious diseases and microbiology at the University of Pittsburgh Graduate School of Public Health in Pennsylvania — and colleagues have published their findings in the journal EBioMedicine.

Using an entirely different virus to target HIV

Mailliard explains the motivation for their study, saying, “A lot of scientists are trying to develop a cure for HIV, and it’s usually built around the ‘kick and kill’ concept — kick the virus out of hiding and then kill it.”

He adds, “There are some promising therapies being developed for the kill, but the holy grail is figuring out which cells are harboring HIV so we know what to kick.”

In the case of HIV, the virus goes latent by hiding itself in the DNA of T helper immune cells.

To find out which cells are harboring HIV, the team decided to look at a different virus with a similar behavior that affects 95 percent of people living with HIV: cytomegalovirus (CMV).

“The immune system spends a lot of time keeping CMV in check,” explains study co-author Charles Rinaldo, Ph.D., chair of the Department of Infectious Diseases and Microbiology at the University of Pittsburgh.

“In some people, 1 one out of every 5 T cells are specific to that one virus,” adds Rinaldo. “That got us thinking — maybe those cells that are specific to fighting CMV also make up a large part of the latent HIV reservoir.”

“So we engineered our immunotherapy to not only target HIV but to also activate CMV-specific T helper cells.”

Dragging HIV out of its hiding place

So, the researchers took blood from almost two dozen participants who had HIV but were keeping it in check with antiretroviral therapy.

“You have to collect a lot of blood to find T cells latently infected with functional HIV in people on [antiretroviral therapy] — it could be as few as 1 out of every 10 million cells,” explains first study author Jan Kristoff.

The researchers also isolated another type of immune cell called dendritic cells. Mailliard describes these cells using a sports analogy; they are the “quarterbacks” of the immune system, he says, as “they hand off the ball and dictate the plays, telling other immune cells where to go and what to fight.”

In previous studies, scientists used dendritic cells to “make” the immune system kill HIV. Before this study, however, nobody had used them to drag the latent HIV out of its hiding place.

In this research, Mailliard and his team designed “antigen-presenting type 1-polarized, monocyte-derived dendritic cells” (MDC1). They engineered these MDC1 cells to look for and activate CMV-specific T helper cells in the hope that these CMV-specific cells would also hide latent HIV.

Then, the team added MDC1 back to the T helper cells containing latent HIV. This successfully reversed the latency. The virus had to leave its hiding place, making it vulnerable and easy to kill.

“Without adding any other drug or therapy,” explains Mailliard, “MDC1 were then able to recruit killer T cells to eliminate the virally infected cells.”

With just MDC1, we achieved both kick and kill — it’s like the Swiss Army knife of immunotherapies. To our knowledge, this is the first study to program dendritic cells to incorporate CMV to get the kick, and also to get the kill.”

Robbie Mailliard, Ph.D.

Mailliard and his colleagues are now trying to test MDC1 in human clinical trials.

Recent Posts

  • Researchers at the Technion–Israel Institute of Technology have developed a glue gun to put the human body back together when it has been seriously injured. The pins and stitches currently used to treat serious injuries come with drawbacks: They can be painful, they leave scars, they require high skill from the doctor, and they sometimes have to be removed after the tissues heal. Suture on the intestine, lungs or blood vessels often leak and therefore require a sealant. The medical glue that the researchers have developed is a “two in one,” said Prof. Boaz Mizrahi, head of the Biomaterials Laboratory of the Technion. It replaces both stitches and the sealant, and is good for both external and internal injuries, he said. All sorts of medical glues are already being used in dermatology, surgery, and other areas. Israeli startup Nanomedic Technologies Ltd., for example, has developed a medical device that it says can dress burns and other wounds with nano materials that mimic human tissue and peel off once the skin below is regenerated. Still, the glues currently in use to replace sutures and staples are limited by their mechanical properties and toxicity, the researchers said. Because they are very toxic, they can be utilized only on the surface of the skin. In addition, hardening of the glue may make the organ less flexible or the adhesion may not be sufficiently strong. With these limitations in mind, researchers have been on the hunt for a glue that is suitable for different tissues, nontoxic, and flexible after hardening. Such a glue would also need to decompose in the body after the tissue is fused together. Mizrahi worked together with doctoral student Alona Shagan and came up with what they say is a “very strong, nontoxic tissue adhesive that remains flexible even after solidification.” Their study...
  • Pinnacle Ventures has launched a pharmacogenomics programme to enable genetic testing to drive personalised prescribing decisions. The innovation arm of Pinnacle Midlands Health Network, a not-for-profit primary health care management company in New Zealand, is also working on embedding biomarker information into electronic health records and linking it to a clinical-decision support prescribing tool that can help prescribers by providing direct access to international pathways and guidelines. Pharmacogenetics involves prescriptions being tailored to a person’s genetic make-up, as people metabolise drugs in different ways, which can have a significant impact on a drug’s effectiveness. Ventures plans to do about 5,000 pharmacogenetic tests over the next 12 months, says chief executive John Macaskill-Smith. Some will be self-funded because individuals are struggling with their medications and others will be fully funded by Ventures, targeting specific groups within the Midlands population. Macaskill-Smith says it is a simple test that covers 65–70 per cent of medications frequently prescribed in New Zealand. “The New Zealand health system is under strain but using testing like this you could reduce the trial and error of prescribing and prevent adverse reactions to medications,” he said. Ethnicity plays a big part in how a person metabolises drugs, but the clinical trials that prescribing information are based on very rarely involve Māori or Pasifika test subjects. Macaskill-Smith said Ventures is partnering with key kiwi groups, Auckland University and Otago University medical schools and Callaghan Innovation to support research and develop a better understanding of how unique New Zealand populations respond to different medications. People who have a pharmacogenetic test can choose to consent to contributing their non-identifiable demographic information to researchers. Embedding the biomarker information into EHRs ensures a patient’s results are used for both current and future prescribing decisions, he said. Macaskill-Smith says a lot of direct-to-consumer online genetic-testing tools involve people...
  • Surgery students spend so much time on screens that they have lost the ability to perform simple tasks such as stitching and sewing up patients, a professor has warned. Roger Kneebone, a professor of surgical education at Imperial College, London, says the focus on academic knowledge has come at the expense of craftsmanship. “It is important and an increasingly urgent issue,” Kneebone told the BBC. “It is a concern of mine and my scientific colleagues that whereas in the past you could make the assumption that students would leave school able to do certain practical things – cutting things out, making things – that is no longer the case.” The professor, who teaches surgery to medical students, believes that this is down to an increase in technology which takes away the experience of handling materials and developing skills. ”An obvious example is of a surgeon needing some dexterity and skill in sewing or stitching,” he explained. ”A lot of things are reduced to swiping on a two-dimensional flat screen” Kneebone adds that a growing number of students are becoming “less competent and less confident” in using their hands, resulting in young professionals who “have very high exam grades but lack tactile general knowledge”. The professor will be speaking on Tuesday at the V&A Museum of Childhood in east London, at the launch of a report, published by the Edge Foundation, calling for more creativity in the curriculum. The report warns that entries to creative subjects have fallen by 20 per cent since 2010, including a 57 per cent fall in design and technology GCSE. Tristram Hunt, director of the Victoria and Albert Museum, who will be speaking alongside Professor Kneebone added: “Creativity is not just for artists. “Subjects like design and technology, music, art and drama are vitally important for...