Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated

Abstract

Background. The live respiratory syncytial virus (RSV) candidate vaccine LIDcpδM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods. RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpδM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results. Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had =4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%).