In this work, a vaccine vector has been engineered that uses potent features of adenovirus that normally infects respiratory tissues and of reovirus that infects the mucosal membranes of the gut. To develop this potential vaccine vector, a key protein of reovirus that allows it to enter the gut has been exchanged into adenovirus to retarget this non-infectious gene therapy vector into mucosal surfaces.
"This mucosal targeting vector may prove quite potent for repelling viruses like HIV-1 and infectious bioweapons, since the vast majority of pathogens enter the body at mucosal surfaces," said Dr. Michael Barry, an associate professor in BCM's Center for Cell and Gene Therapy with a joint appointment in the Department of Bioengineering at Rice University.
"We will first test this as an HIV vaccine in mice." said George T. Mercier, a Rice University Bioengineering graduate student working with Barry, who serves as his advisor. "If it's useful for HIV-1, it may be useful for a wide variety of other pathogens since you can put any vaccine gene you want into this vector."
"Beyond its potential as a vaccine vehicle, this hybrid vector will also have utility by allowing us to study the specific interactions of this reovirus protein in the host," said Barry. "This has previously been difficult due to the complex genetics of reovirus. Now we can study these complex interactions using the simpler genetic system provided by the adenoviral vector."
Collaborators include: Terence S. Dermody, Jacquelyn A. Campbell and James D. Chappell of Vanderbilt University School of Medicine in Nashville, Tennessee, and Thilo Stehle of Harvard Medical School in Boston.
Journal
Proceedings of the National Academy of Sciences