Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated.

Background. The live respiratory syncytial virus (RSV) candidate vaccine LIDcp Delta M2-2 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 LIDcp Delta M2-2 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 log(10) PFU/mL by quantitative culture and 4.5 log(10) 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%). Conclusions. RSV LIDcp Delta M2-2 is overattenuated. Clinical Trial Numbers. NCT02890381, NCT02948127.