Live-attenuated respiratory syncytial virus vaccine candidate with deletion of RNA synthesis regulatory protein M2-2 is highly immunogenic in children

Background. Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication. Methods. RSV-seronegative children ages 6–24 months received a single intranasal dose of 10 ⁵ plaque forming units (PFU) of LIDΔM2-2 (n = 20) or placebo (n = 9) (NCT02237209, NCT02040831). RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. During the following RSV season, participants were monitored for respiratory illness and pre- and post-RSV season serum antibodies. Results. Vaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log ₁₀ PFU/mL by quantitative culture and 6.3 log ₁₀ copies/mL by PCR); 90% had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common in vaccine (95%) and placebo (78%). One vaccinee had grade 2 rhonchi concurrent with vaccine shedding, rhinovirus, and enterovirus. Eight of 19 vaccinees versus 2 of 9 placebo recipients had substantially increased RSV antibody titers after the RSV season without medically attended RSV disease, indicating anamnestic vaccine responses to wild-type RSV without significant illness. Conclusion. LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion. Clinical Trials Registration. NCT02237209, NCT02040831.