August 22, 2016
Baltimore-based scientists awarded grant to solve a major challenge in HIV-1 vaccine research
The Institute of Human Virology (IHV) at the University of Maryland School of Medicine announced today a $14.4 million grant from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) to tackle a significant scientific global challenge in HIV vaccine research – the inability to produce long-lasting antibodies to protect against HIV infection. The announcement was made today by Robert C. Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor of Medicine, Director, Institute of Human Virology, University of Maryland School of Medicine, and his colleagues George Lewis, PhD, Professor of Microbiology and Immunology, Director Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine and Anthony DeVico, PhD, Professor of Medicine, Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine. IHV’s grant collaborators include Guido Silvestri, MD at the Yerkes National Primate Research Center of Emory University and Warner Greene, MD, PhD, of the Gladstone Institute of Virology & Immunology at the University of California at San Francisco.
"Since our group co-discovered HIV as the cause of AIDS in the early 1980’s, I have long stated that any successful vaccine would need to block HIV infection from the start given the nature of retroviruses and HIV’s aggressive replication cycle," said Dr. Gallo, who pioneered the field of human retroviruses with his 1980 discoveries of the first human retroviruses (Human T cell Leukemia-1, or HTLV-1 and Human T cell Leukemia-2, or HTLV-2). "In order to do this, we must have persistent antibodies to protect against HIV."
HIV vaccine development presents unprecedented challenges on multiple levels, a reality, often overlooked, that cannot be overstated. The chief challenge is that HIV is a human retrovirus that replicates by irreversibly inserting its genes into the host genome. Thus, HIV infection is established permanently in a matter of days or perhaps even hours (1–6), and it cannot be cleared by primary or anamnestic responses that occur after exposure. In addition to integrating into the host genome, a second unique challenge is that HIV replicates in CD4+ T cells that are key players in protective immunity not only to HIV itself but also too many other pathogens. These central features distinguish the path to an HIV vaccine from the traditional design principles that led to successful vaccines against other infectious agents.[1]
"While we study the antibody sustainability problem, we need to activate T cells that fight HIV,” said Dr. Lewis. “However, T cells are also the very cells that HIV infect and kill. Thus, there is a fine balance we must reconcile so that we can examine and produce long-lasting antibodies for an effective vaccine."
Last fall, IHV launched Phase 1 clinical trials of a novel HIV vaccine candidate developed by Drs. Gallo, Lewis, DeVico and Tim Fouts, PhD of Baltimore-based Profectus Biosciences, Inc., a spinoff company from IHV. The candidate immunogen, denoted as the Full-Length Single Chain (FLSC), is designed to elicit strong protective antibody responses across the spectrum of HIV-1 strains. The IHV team will utilize the FLSC as a model system with the goal of finding ways to improve the efficacy and durability of all HIV vaccines.
"We have noticed an unusual, but not uncommon, phenomenon in HIV’s envelope protein that affects the sustainability of antibodies,” said Dr. DeVico. "We need to learn why this is happening so we can promote durability in our vaccine’s antibody response against HIV."
"We believe this antibody durability challenge is solvable,” said Dr. Gallo. "Importantly, funding sources and collaborators such as NIAID and The Bill & Melinda Gates Foundation are critical partners in our quest to solve this complex scientific challenge and we are grateful for their continued support, among others."
About the Institute of Human Virology
Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland and the University of Maryland Medical System, IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders - most notably, HIV the virus that causes AIDS. For more information, visit www.ihv.org and follow us on Twitter @IHVmaryland. You may also view a video about the IHV: http://ow.ly/T7Isr
[1] Lewis GK, DeVico AL, Gallo RC. Antibody persistence and T-cell balance: two key factors confronting HIV vaccine development. Proc Natl Acad Sci U S A. 2014;111(44):15614-21. doi: 10.1073/pnas.1413550111. PubMed PMID: 25349379; PMCID: 4226080.
Contact
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newsletter@som.umaryland.edu
Nora Samaranayake
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