The closing plenary session of ID Week 2017 looked ahead to the fight against infectious diseases. James Crowe, Jr, MD, Vanderbilt University Medical Center, Nashville, Tennessee, struck an optimistic note. “I believe we are in the midst of a sea change in moving from antibiotics to antibodies to combat infectious diseases,” he said.
Traditional vaccine development is a laborious failure-and-success process that can take decades. The old timetable just won’t work any longer. “Antibody technology is mature enough and affordable enough to now be considered as a first approach,” said Dr. Crowe. The path from the discovery of an antigenic target to antibody availability is measured in months, not decades. Formulations with half-lives of up to 90 days are being developed. The manufacture of antibodies and their safe administration is well established. All these facts argue for antibody-based strategies as the go-to tool in infectious diseases.
Structure-based vaccines (reverse vaccinology) have been a research goal for decades. The approach identifies an antibody to the microbe of concern and then works backward to identify the epitope. The strategy has been successful in proof-of-concept studies for the Marburg, Ebola, influenza, Zika, chikungunya, and dengue viruses.
To this end, Dr. Crowe is spearheading the Human Immunome Program that audaciously seeks to determine the sequence of every antibody and T-cell receptor. The immunome is the complete set of recombined immune receptor genes. The human genome with its 20,000-30,000 genes pales in comparison to the genetic complement of the immunome, which may be 1012
or more greater numerically. It’s an immense project, but the potential payoffs are equally immense. The work would clarify how antigenic reservoirs are stable (or not) over time; antigenic targets that are fruitful for vaccine development and those (like autoimmune-associated epitopes) that should be avoided; and how diseases change the terrain of the immunome.
New tools not only have the potential of disease therapy; they can be harnessed for the eradication of microbial pathogens. This aspect of 21st-century infectious disease was discussed by Christopher Karp, MD, Director of Global Health Discovery and Translational Sciences at the Bill and Melinda Gates Foundation (BMGF), Seattle, WA.
The BMGF global health-related programs include the eradication of polio and malaria. The job with polio is not done, even with the historic success of the Salk and Sabin vaccines. Global hotspots remain, which can be the seed for a resurgence of the disease. Efforts have resulted in the improved genetic stability of the Sabin virus strain, with the first-in-human clinical trial that began in May 2017.