Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children
Year: 2018
Type: article
Abstract: 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 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. Results: Vaccine 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. Conclusion: LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion. Clinical Trials Registration: NCT02237209, NCT02040831.
Authors: 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
Institutions: Children's Hospital Colorado, University of Colorado Anschutz, Johns Hopkins University, Harvard University, Duke Medical Center, Family Health International 360, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Johns Hopkins Hospital, Northwestern University, Lurie Children's Hospital, University of California San Diego, Rush University Medical Center, St. Jude Children's Research Hospital, University of Southern California
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2789458933