Your Avant-Garde award—awarded in 2011—was given for the project entitled “Monthly Antiretroviral Therapy Using Multispecific HIV Neutralizing Antibodies.” What was your vision for this concept?
We wanted to engineer a library of antibodies that would have unique and favorable properties in blocking HIV infection in vitro. All of these bispecific antibodies were constructed with one arm directed at the virus receptor CD4, and with the other arm directed to the virus glycoprotein gp160. The goal is to identify one or several antibodies that would have potent and broad neutralizing activity against a large panel of HIV strains. Since antibodies have favorable pharmacokinetic profiles, our antibodies could become candidate antiviral agents that may be administered on a monthly basis, thereby offering an alternative way of treating HIV infection in the future.
How has the award helped you advance this area of science?
With the NIDA funding, we were able to generate a library of over 100 bispecific antibodies, and we have identified several with potency about 100-fold greater than any monovalent antibody described to date. Moreover, the breadth of our top antibody candidates is nearly 100%.
Have there been any surprises or unusual challenges along the way?
We were favorably impressed with the potency of our top bispecific antibodies, and we are trying to understand the underlying scientific basis for the exceptional potency. The challenge we did not anticipate was the instability of the bispecific antibodies. This problem prompted us to create variants of our top bispecific antibodies in order to find ones that are both potency/broad and stable. We now have stable variants in hand.
What advice would you give to others seeking similar awards for bold and innovative science?
The Avant Garde Award encourages one to pursue high-risk but high-yield ideas. There are not too many such funding opportunities at NIH. Take advantage of this program; be bold and seize this opportunity.
Where will your vision of HIV/AIDS research take you next?
Our bispecific antibodies have the product profile for monthly HIV therapy, and we are now taking one or two of them forward into clinical development.