Respiratory Syncytial Virus (RSV) is the major cause of
pneumonia among infants. Here we elucidated the antibody repertoire following primary
RSV infection and traced its evolution through adolescence and adulthood. Whole genome-fragment phage display libraries (GFPDL) expressing linear and conformational
epitopes in the RSV fusion
protein (F) and
attachment protein (G) were used for unbiased
epitope profiling of infant sera prior to and following
RSV infection. F-GFPDL analyses demonstrated modest changes in the anti-F
epitope repertoires post-
RSV infection, while G-GFPDL analyses revealed 100-fold increase in number of bound phages. The G-reactive
epitopes spanned the N- and C-terminus of the G ectodomain, along with increased reactivity to the central conserved domain (CCD). Panels of F and G antigenic sites were synthesized to evaluate sera from young children (<2 yr), adolescents (14-18 yr) and adults (30-45 yr) in SPR real-time kinetics assays. A steady increase in RSV-F
epitope repertoires from young children to adults was observed using
peptides and F
proteins. Importantly, several novel
epitopes were identified in pre-fusion F and an
immunodominant epitope in the F-p27. In all age groups, antibody binding to pre-fusion F was 2-3 folds higher than to post-fusion form. For RSV-G, antibody responses were high following early
RSV infection in children, but declined significantly in adults, using either
G proteins or
peptides. This study identified unlinked evolution of anti-F and anti G responses and supportive evidence for immune pressure driven evolution of RSV-G. These findings could help development of effective countermeasures including
vaccines.