Scientific Publications by FDA Staff

J Infect Dis 2020 Feb 3;221(4):636-46

Antigenic fingerprinting of RSV-A infected hematopoietic cell transplant recipients reveals importance of mucosal anti-RSV-G antibodies in control of RSV infection in humans.

Fuentes S, Hahn M, Chilcote K, Chemaly RF, Shah DP, Ye X, Avadhanula V, Piedra PA, Golding H, Khurana S

BACKGROUND: Respiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplants (HCT) patients. However, antibody response that correlate with recovery from RSV disease are not fully understood. METHODS: In this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A infected HCT patients who recovered early (<14 days RSV shedding) were compared with late-recovered patients (>14 days shedding) using gene fragment phage display libraries (GFPDL) and surface plasmon resonance (SPR). RESULTS: Anti-F serum response were similar between these two groups for antibody repertoires, neutralization titers, anti-F binding antibodies (pre-fusion and post-fusion proteins), antibody avidity and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV-G antibody repertoires in the two groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain (CCD). Most importantly, a significantly higher antibody affinity to RSV-G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT patients. CONCLUSIONS: These findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.