Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children
| Autor: | Jennifer Libous, Cindy Luongo, Laura Fearn, Lijuan Yang, Petronella Muresan, Elizabeth Schappell, Coleen K. Cunningham, Ruth A. Karron, Charlotte Perlowski, Elizabeth J. McFarland, Mikhaela Cielo, Patrick Jean-Philippe, Emily Barr, Jack Moye, Vivian Rexroad, Peter L. Collins, Andrew Wiznia, Jaime G. Deville, Jennifer Oliva, Ursula J. Buchholz |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adolescent viruses Respiratory Syncytial Virus Infections Antibodies Viral Vaccines Attenuated Virus Immunoglobulin G Viral Proteins Major Articles and Brief Reports 03 medical and health sciences 0302 clinical medicine Respiratory Syncytial Virus Vaccines Humans Immunology and Allergy Medicine 030212 general & internal medicine Child Reactogenicity biology business.industry Immunogenicity Antibody titer virus diseases respiratory system Antibodies Neutralizing Virology Titer 030104 developmental biology Infectious Diseases Respiratory Syncytial Virus Human biology.protein RNA Small Untranslated RNA Viral Antibody business Hydrophobic and Hydrophilic Interactions Gene Deletion |
| Zdroj: | J Infect Dis |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Background Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. Methods RSV-seronegative children aged 6–24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. Results All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. Conclusions D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. Clinical Trials Registration NCT03102034 and NCT03099291. |
| Databáze: | OpenAIRE |
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