“This laboratory-engineered molecule blocks two key receptors that the human immunodeficiency virus (HIV) uses to gain entry to the body’s CD4 white blood cells,” said Ronald C. Desrosiers, Ph.D., professor of pathology at the University of Miami Miller School of Medicine. “The study shows that 100 percent of HIV-1 strains are neutralized by this new inhibitor – the first time that this level of protection has been accomplished.”
Michael Farzan, Ph.D., professor of infectious diseases at Scripps Florida in Jupiter, was the senior author of the study, “AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges,” published online this week in Nature. Miller School coauthors were Desrosiers, Sebastian P. Fuchs, Ph.D. candidate, and Jose M. Martinez-Navio, Ph.D., assistant scientist in the Pathology Department. The study’s other co-authors were from 12 medical schools, research institutions and laboratories in the U.S. and France.
Desrosiers and Farzan were colleagues at Harvard Medical School before Farzan joined Scripps and Desrosiers joined the Miller School in 2013. Desrosiers said the Scripps Florida researchers took an innovative approach to protecting against HIV-1, which uses two separate receptors, CD4 and CCR5, in a sequential fashion to gain entry into a cell.
“Some HIV-infected people develop unusual but highly potent antibodies that can be replicated in a laboratory,” Desrosiers said. “Dr. Farzan found a creative way to assemble portions of these antibody-like molecules in a manner that results in potent antiviral activity in attacking HIV-1.”
In the collaborative study, Desrosiers focused on using an adeno-associated virus (AAV) vector system to deliver the HIV-blocking molecules via muscle cells, which can then act as long-term “factories” that produce antibodies in the event of future HIV exposure. “We were able to demonstrate that the AAV method was effective in delivering the biological agent to monkeys, protecting against subsequent exposure to the AIDS virus,” Desrosiers said.
While at Harvard, Desrosiers discovered the simian immunodeficiency virus (SIV), the closest known relative of HIV found in monkeys. He is the author of nearly 300 peer-reviewed papers, and has received numerous awards and honors over his career, including 2002’s “Most Highly Cited Scientist.”
Both Farzan and Desrosiers are members of the University of Miami Center for AIDS Research (CFAR), which is one of 20 U.S. centers funded by the National Institutes of Health. “We are collaborating on new studies that involve delivery of antibodies and this antibody-like inhibitor, which have the potential of providing a vaccine-like solution to long-term protection against HIV,” Desrosiers said.
Miller School Departments, Centers and Institutes