• Elizabeth J McFarland, Ruth A Karron, Petronella Muresan, Coleen K Cunningham, Megan E Valentine, Charlotte Perlowski, Bhagvanji Thumar, Devasena Gnanashanmugam, George K Siberry, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Ram Yogev, Stephen A Spector, Mariam Aziz, Nehali Patel, Mikhaela Cielo, Cindy Luongo, Peter L Collins, Ursula J Buchholz, and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2000 Study Team.
• Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora.
• J. Infect. Dis. 2018 Apr 11; 217 (9): 1347-1355.

BackgroundLive 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.MethodsRSV-seronegative children ages 6-24 months received a single intranasal dose of 105 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.ResultsVaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log10 PFU/mL by quantitative culture and 6.3 log10 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.ConclusionLIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion.Clinical Trials RegistrationNCT02237209, NCT02040831.

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