Reverse genetics systems for contemporary isolates of respiratory syncytial virus enable rapid evaluation of antibody escape mutants

Significance Respiratory syncytial virus (RSV) remains a major cause of severe respiratory disease worldwide in children, older individuals, and immunosuppressed patients. An increasing understanding of this disease burden together with the absence of an effective vaccine and limited therapeutic options has resulted in many new preclinical and clinical studies into novel vaccines, antibodies, and antivirals. This requires complementary expansion of the RSV molecular toolkit to encompass reverse genetics systems based on contemporary strains. We show that full-length cDNA clones of recent strains are most stable when a bacterial artificial chromosome is used as the vector backbone. This enabled recombinant viruses encoding antibody escape mutations to be generated and assessed with respect to antibody escape and capacity to induce cell-to-cell fusion.