Emily Moser, PhD

Influenza A virus is a serious global health threat, causing approximately 36,000 deaths per year in the United States alone. The primary intervention against influenza infection is vaccination to induce protective antibodies. Programming of the antibody response occurs in specialized niches in lymphoid tissue called germinal centers. Vaccines are less effective in certain groups with weakened germinal center responses, such as elderly and immunocompromised individuals. We have discovered that the enzyme Cul4b is essential for germinal center expansion and formation of protective antibody responses. Our research will define the role of Cul4b in germinal center and antibody responses after influenza vaccination. Results from these studies will aid in the design of new vaccines that enhance the Cul4b pathway, unleashing robust antibody responses in populations with weakened immune systems.

Update:
We have discovered a novel pathway in immune cells called B cells that promote protective immunity against influenza A virus. The enzyme Cul4b promotes antibody formation after both infection and vaccination with influenza virus. Our latest results show that B cell Cul4b promotes proliferation and survival after DNA damage associated with somatic hypermutation, a process that allows B cells to mutate the genes that they use to produce antibodies. In this way, Cul4b facilitates strong-bonding antibody formation, rapid virus clearance, and long-term protection.

Final Project Update: 
Influenza A virus poses a serious global health risk, causing around 36,000 deaths each year in the United States. Vaccination is the main defense to trigger protective antibodies. Programming of the antibody response occurs in specialized niches in lymph tissue called germinal centers. Vaccines are less effective in certain groups with weakened germinal center responses, such as elderly and immunocompromised individuals. 

Our research has shown that the enzyme Cul4b is crucial for germinal center growth and the development of effective antibody responses. Cul4b aids in the proliferation of germinal center B cells while they undergo DNA damage necessary for improving antibody quality after vaccination. 

Future studies will explore the molecular pathways involving Cul4b in B cells, their role in B cell function, and how these pathways can be targeted to enhance vaccine responses. New adjuvants that stimulate these networks in B cells could be used to boost antibody levels and effectiveness for individuals with weakened immune systems against influenza and other respiratory infections.