We interviewed the Principal Investigators responsible for leading each of the CIVICs Centers as part of a two part interview series. In the first part of this article, we learned about Tony Moody, the Principal Investigator of the Duke CIVIC Vaccine Center (DCVC). This article provides an introduction to DCVC and CIVICs from Dr. Moody’s perspective.
What is CIVICs?
If you had to make an elevator pitch for CIVICs, what would you say?
The CIVICs program is aimed at making better vaccines for influenza with the ultimate goal of making a universal vaccine. We would love to create a vaccine that can be given early in life, not require boosting, and that would provide life-long protection, similar to the measles vaccine. There are many reasons why that is a very challenging problem for influenza, but the CIVICs program is set up to tackle those problems. Along the way, we expect to make better vaccines than the ones we currently have, and the CIVICs programs will work toward making and testing those vaccines as well. If we can improve on what is done currently, either by needing less frequent boosters, providing broader protection, or by overcoming some of the limits of current vaccines, that will be a win.
Tell me the origin story of your Center.
The DCVC is one of the three vaccine centers charged with discovering new vaccine candidates to solve these problems. The DCVC is probably perceived as the mRNA program because we are lucky enough to have Drew Weissman as a member and collaborator. And while we are very pleased to have Drew, we are looking at multiple platforms and approaches because we think there may be advantages to other ways of doing things. One major focus is on understanding how the immune response gets imprinted by early influenza exposure, a phenomenon called “original antigenic sin” by some, and then how can we use vaccines to overcome potential problems created by imprinting. In addition, we are interested in developing approaches that leverage some of the unique aspects of the platforms we have in DCVC, such as the mRNA vaccine approaches pioneered by Drew Weissman and Katalin Karikó or the inactivation techniques of our partners at Najít Technologies.
The DCVC grew out of a number of collaborations that were going on for many years prior to the CIVICs program application process. Many of these collaborations started in the HIV-1 field, specifically as part of the Center for HIV/AIDS Vaccine Immunology (CHAVI) program under Bart Haynes who has been my mentor and collaborator for many years. We started doing influenza work in that program really as a control, using another diverse viral infection to help us understand what was going on in the immune system. What grew out of that program was a collaboration between Bart, myself, Greg Sempowski, Garnett Kelsoe, and Larry Liao at Duke, and Steve Harrison at Boston Children’s Hospital—that led to a P01 program that is ongoing to this day.
The P01 program under Steve Harrison led to the description by Aaron Schmidt of some of the molecular mechanisms of imprinting to influenza and demonstrated how those responses evolved over lifetime influenza exposures. While all of this was going on, the CHAVI program also developed a relationship with Drew Weissman to leverage the mRNA platform for HIV-1 vaccine development. So when the CIVICs program application process started, it seemed natural to bring all of these elements together to form the DCVC. We were fortunate to have more great collaborators at Duke, like Nick Heaton who is modifying influenza viruses to make new vaccines and Georgia Tomaras who has extensive experience in the analysis of clinical trials. Since launching, the DCVC has continued to build this network and we are now lucky to have six new collaborators who have joined since our launch: Fan Yuan (Duke), Ian Amanna (Najít Technologies), Kevin McCarthy (Pitt), Joel Collier (Duke), Scott Hensley (UPenn), and Martha Alexander-Miller (Wake Forest).
Explain the scientific aims of your Center to me but pretend I’m a high schooler.
Tell me about an exciting recent discovery from your CIVICs Center.
There’s a lot going on but some of it I can’t talk about just yet or can’t be too specific (patent considerations). Some of the platform development work at Najít is looking very promising to improve virus inactivation while preserving virus structure. The hyperglycosylation approach by Aaron Schmidt looks promising as a way to direct the immune response to certain broadly protective responses. One thing I’m particularly excited about is what looks to be a new, broadly reactive epitope that we’ve found on hemagglutinin with hints that it could provide very broad reactivity. We have lots more work to do to nail it down, but if everything pans out, it could be a big deal.
If you had to recommend another person from your Center for me to interview, who would it be, and why?
If you can get him, Drew Weissman would be a great one to talk to given everything that’s gone on over the last two years. I also think Mark Slifka and Ian Amanna at Najít could provide an insight into what it’s like to join the program while in progress.