A major new federal grant is set to advance research into respiratory immunity at the University of Virginia, where Harrison Distinguished Teaching Professor Jie Sun, PhD, has been awarded a $3.8 million from the National Institutes of Health.
The funding supports a five-year project titled “Decoding Cellular Networks Governing Respiratory Mucosal IgA Immunity,” aimed at uncovering how the body builds immune defenses in the respiratory tract following infection or vaccination.
Sun, who serves in the Department of Medicine’s Division of Infectious Diseases and International Health and Co-Directs the Beirne B. Carter Center for Immunology Research, said the work targets a critical gap in current immunology.
“Despite advances in vaccines and therapeutics, we still lack a clear understanding of how strong mucosal immunity—especially IgA responses—is generated in the respiratory system,” Sun said. “That knowledge is essential for designing the next generation of vaccines.”
Addressing a Key Immunity Gap
Respiratory mucosal immunity, particularly involving immunoglobulin A (IgA), plays a frontline role in defending against airborne pathogens. However, the biological mechanisms that drive robust IgA responses after infection or vaccination remain poorly understood.
This gap has become increasingly important in the wake of evolving respiratory viruses such as COVID-19 and its variants, where improved mucosal protection could significantly reduce transmission and severity.
The NIH-funded R01 project is built around the central hypothesis that effective respiratory immunity depends on localized interactions among pulmonary macrophages, CD4 T cells, and B cells within the lungs and airways.
Three Research Aims
The study will pursue three major objectives:
- Identify how respiratory CD4+ T cells promote IgA production directly within lung tissues.
- Examine how TGFβ-dependent interactions between macrophages and B cells regulate mucosal IgA responses.
- Define the molecular and functional characteristics of cross-reactive IgA-producing B cells that can respond to multiple respiratory pathogens.
Researchers believe these insights could pave the way for vaccines that provide stronger, longer-lasting protection at the site where infections begin.
Collaborative Effort
The project brings together a multidisciplinary team across UVA. Collaborators include:
- In Su Cheon, PhD, Division of Infectious Diseases and International Health
- Chongzhi Zang, PhD, Department of Genome Sciences
- Justin Taylor, PhD, Division of Infectious Diseases and International Health
Implications for Future Vaccines
By decoding the cellular networks that drive mucosal immunity, the research could inform the development of next-generation vaccines designed not only to prevent severe illness but also to block infection at the point of entry.
Such advances may prove critical in combating emerging respiratory threats, including new variants of SARS-CoV-2 and other airborne pathogens.
“This work has the potential to reshape how we approach vaccine design,” Sun said. “Ultimately, our goal is to enhance protection at the mucosal level and strengthen public health defenses against respiratory diseases.”