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 by Robert C. Gallo, MD, the Homer & Martha Gudelsky Distinguished Professor of Medicine, and director, Institute of Human Virology, and his IHV colleagues George Lewis, PhD, professor, Department of Microbiology and Immunology, director of the Division of Vaccine Research, and Anthony DeVico, PhD, professor, Department of Medicine in the Division of Vaccine Research. 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 1980s, 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 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 to 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.
"While we study the antibody sustainability problem, we need to activate T cells that fight HIV,” said 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 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 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 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."