Bill & Melinda Gates Foundation

Each year, diarrhea—usually a symptom of an infection in the intestinal tract—kills about 525,000 children under the age of 5, according to the World Health Organization. But while successful vaccination represents the most expeditious and practical way to reduce the impact of these infections in the developing world, a major obstacle remains: Oral vaccines do not provide the same level of protection in low-income settings as they do in high-income settings.

Experts cite many potential reasons for this poor immune response—for example, intestinal inflammation or gut microbiome alterations resulting from lifestyle-related or environmental factors. Whatever the reasons, Ulrich von Andrian, MD, PhD, Edward Mallinckrodt Jr. Professor of Immunopathology in the Blavatnik Institute at Harvard Medical School and director of the Center for Immune Imaging at HMS, along with investigators from the University of Washington and the Massachusetts Institute of Technology, formed the Mucosal Vaccine Consortium (MVC) five years ago to develop a non-oral vaccine to protect the lining of the intestines, or intestinal mucosa, which functions as a physical and immunological defense barrier.

Fast forward to today, and the MVC has identified a nanoparticle-based vaccine candidate that elicits the desired mucosal immune response in mouse studies. Von Andrian will further optimize, test, and characterize the consortium’s vaccine modality in rodent models thanks to a $1.1 million grant from the Bill & Melinda Gates Foundation. The foundation, which has been fighting poverty, disease, and inequity around the world for more than 20 years, previously gave nearly $2.7 million to von Andrian for this work and has committed more than $6 million in total to the consortium.

“As this project progresses from the basic research and discovery phase to a focus on developing and optimizing our candidate nanoparticles, it can be more difficult to finance with traditional funding mechanisms,” von Andrian says. “The ongoing support from the Gates Foundation is essential to allow this work to proceed.”

Anastazia Older Aguilar, program officer for vaccine discovery at the Gates Foundation, says mucosal targeting is important across most of the foundation’s priority pathogens, but it has found few adjuvant candidates that can direct mucosal immune responses. An adjuvant is an ingredient Global health and service Diarrhea kills more children every day than AIDS, malaria, and measles combined, according to the Centers for Disease Control and Prevention.used in some vaccines that enhances the body’s immune response to an antigen. “Dr. von Andrian’s program may provide a way to overcome this challenge by adding mucosal targeting signals to vaccines, without the requirement of a healthy gut immune response in the individual to develop those signals,” she says.

Von Andrian says the ongoing work focuses specifically on nanomaterials provided by collaborators at MIT, illustrating the importance of team science in advancing this vaccine project. “The synergistic combination of unique technical and scientific expertise in nanotechnology at MIT and immunology at HMS is critical to bring this project to fruition,” he says.