New Combination Immunotherapy Plus ART Expand Innate Cells Critical to Controlling HIV

May 17, 2021

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Lisa Newbern

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Yerkes National Primate Research Center researchers in collaboration with Institut Pasteur have determined a combination immunotherapy of Interleukin-21 (IL-21) and interferon alpha (IFNa) when added to antiviral therapy (ART) is effective in generating highly functional natural killer (NK) cells that can help control and reduce simian immunodeficiency virus (SIV) in animal models. This finding, published online in Nature Communications, is key for developing additional treatment options to control HIV/AIDS, which impacts 38 million people worldwide.

ART is the current leading treatment for HIV/AIDS. It is capable of reducing the virus to undetectable levels, but is not a cure and is hampered by issues such as cost, adherence to medication treatment plan and social stigma.

To reduce reliance on ART, the Yerkes, Emory and Institut Pasteur research team worked with 16 SIV-positive, ART-treated rhesus macaques. In most nonhuman primates (NHPs), including rhesus macaques, untreated SIV infection progresses to AIDS-like disease and generates NK cells with impaired functionality. This is in contrast to natural primate hosts of SIV, which do not progress to AIDS-like disease (Huot et al., Nature Communications, 2021). Determining why natural hosts do not progress or how to stop the progression is a critical step in halting HIV in humans.

The researchers compared ART-only treated animals with animals that received ART, IL-21 and IFNa to evaluate how the ART plus combination immunotherapy affected the amount of virus in the animals' tissue.

"Our results indicate the ART plus combo-treated rhesus monkeys showed enhanced antiviral NK cell responses," says first author Justin Harper, PhD. "These robust NK cell responses helped clear cells in the lymph nodes (LN), which are known for harboring the virus and enabling its replication and, therefore, the virus' persistence. Targeting areas where the virus seeks refuge and knowing how to limit replication facilitate controlling HIV," Harper continues. Harper is a senior research specialist and lab manager of the Paiardini research lab.

HIV treatment has historically focused on the role of T cells in immunity. "This proof-of-concept study in rhesus monkeys, which progress to AIDS-like disease in the absence of ART, demonstrates how certain NK cell activity can contribute to controlling the virus," says Mirko Paiardini, PhD. "This opens the door to designing additional treatment strategies to induce SIV and HIV remission in the absence of ART, and, ultimately, reducing the burden HIV is to individuals, families and the world," he adds. Paiardini is an associate professor of Pathology and Laboratory Medicine at Emory University and a researcher at Yerkes.

This study was done in close collaboration with Michaela Müller-Trutwin, PhD, and Nicolas Huot, PhD, at Institut Pasteur. Muller-Trutwin is professor and head of the HIV, Inflammation and Persistence unit, and Huot is a post-doctoral fellow in Muller-Trutwin's laboratory. The Yerkes/Emory research team also included Luca Micci, PhD, Steve Bosinger, PhD, Guido Silvestri, MD, and Kirk Easley, MS. Bosinger is assistant professor, Department of Pathology & Laboratory Medicine, Emory School of Medicine (SOM) and Emory Vaccine Center (EVC); director, Yerkes Nonhuman Primate (NHP) Genomics Core; and a researcher in Yerkes' Division of Microbiology and Immunology. Silvestri is Yerkes division chief, Microbiology and Immunology; Georgia Research Alliance eminent scholar in comparative pathology; and professor and chair, Department of Pathology and Laboratory Medicine, Emory University School of Medicine. Easley is senior associate, Biostatistics and Bioinformatics, Rollins School of Public Health at Emory.

The research reported in this release is supported in part by the by the Yerkes National Primate Research Center base grant from the NIH Office of the Director, Office of Research Infrastructure Programs. The National Institute of Allergy and Infectious Diseases, National Center for Research Resources (through 2015) and National Cancer Institute provided additional funding as did the French National Agency of Research on AIDS and Viral Hepatitis (ANRS), and the Fondation J. Beytout.

Grant amounts (direct + indirect):

  • P51OD011132 $10, 751,414 yr / 5 years
  • R01AI116379 $783,714 yr / 6 years
  • R01AI143457 $659,902 yr / 5 years
  • 5R24RR016988 $510,411 yr / 13 years

Note: The amounts listed above are for the full grants. Only a portion of the P51, R01/379 and R24 grants supported the research reported in this news release.

Dedicated to discovering causes, preventions, treatments and cures, the Emory National Primate Research Center (NPRC), part of Emory University's Robert W. Woodruff Health Sciences Center, is fighting diseases and improving human health and lives worldwide. The center, one of only seven NPRCs the National Institutes of Health (NIH) funds, is supported by more than $74 million in research funding (all sources, fiscal year 2018). Yerkes researchers are making landmark discoveries in microbiology and immunology; neurologic diseases; neuropharmacology; behavioral, cognitive, and developmental neuroscience; and psychiatric disorders. Since 1984, the center has been fully accredited by the AAALAC International, regarded as the gold seal of approval for laboratory animal care. For more information about Yerkes and the seven NPRCs, visit and follow us at @NPRCnews.

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

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