Molecular Dissection Of Human Antibody Responses Following Prefusion-Stabilized RSV F Vaccination

An effective vaccine for RSV is an unrealized public health goal. Recently, a single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) was shown to substantially increase serum neutralizing activity in healthy adults. To understand the induced B-cell repertoire at the single-cell level, we evaluated RSV F-specific B-cell responses before and after vaccination in six participants and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six previously defined antigenic sites on the pre-F trimer. Among the six vaccinees, we identified 34 public clonotypes. Structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Collectively, these findings demonstrate that vaccination with DS-Cav1 generates a diverse polyclonal response targeting all known antigenic sites present on pre-F.