Elizabeth J McFarland1, Ruth A Karron2, Petronella Muresan3, Coleen K Cunningham4, Jennifer Libous5, Charlotte Perlowski5, Bhagvanji Thumar2, Devasena Gnanashanmugam6, Jack Moye7, Elizabeth Schappell2, Emily Barr1, Vivian Rexroad8, Laura Fearn9, Stephen A Spector10,11, Mariam Aziz12, Mikhaela Cielo13, Christy Beneri14, Andrew Wiznia15, Cindy Luongo16, Peter Collins16, Ursula J Buchholz16. 1. Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado, USA. 2. Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 3. Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health/Frontier Science, Boston, Massachusetts, USA. 4. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA. 5. FHI 360, Durham, North Carolina, USA. 6. Maternal, Adolescent and Pediatric Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 7. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. 8. Investigational Drug Service Pharmacy, Johns Hopkins Hospital, Baltimore, Maryland, USA. 9. Department of Pediatrics, Northwestern University Medical School and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA. 10. Department of Pediatrics, University of California San Diego, La Jolla, California, USA. 11. Rady Children's Hospital, San Diego, California, USA. 12. Section of Infectious Disease, Rush University Medical Center, Chicago, Illinois, USA. 13. Division of Infectious Diseases, Maternal Child and Adolescent Center, University of Southern California Keck School of Medicine, Los Angeles, California, USA. 14. Department of Pediatrics, SUNY Stony Brook, Stony Brook, New York, USA. 15. Department of Pediatrics, Albert Einstein College of Medicine and Jacobi Medical Center, Bronx, New York, USA. 16. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Abstract
BACKGROUND: The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. METHODS:Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. RESULTS:Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. CONCLUSIONS: LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
RCT Entities:
BACKGROUND: The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. METHODS:Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. RESULTS: Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. CONCLUSIONS:LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
Authors: P L Collins; M G Hill; E Camargo; H Grosfeld; R M Chanock; B R Murphy Journal: Proc Natl Acad Sci U S A Date: 1995-12-05 Impact factor: 11.205
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 Journal: J Infect Dis Date: 2018-04-11 Impact factor: 5.226
Authors: R A Karron; P F Wright; J E Crowe; M L Clements-Mann; J Thompson; M Makhene; R Casey; B R Murphy Journal: J Infect Dis Date: 1997-12 Impact factor: 5.226
Authors: Ting Shi; David A McAllister; Katherine L O'Brien; Eric A F Simoes; Shabir A Madhi; Bradford D Gessner; Fernando P Polack; Evelyn Balsells; Sozinho Acacio; Claudia Aguayo; Issifou Alassani; Asad Ali; Martin Antonio; Shally Awasthi; Juliet O Awori; Eduardo Azziz-Baumgartner; Henry C Baggett; Vicky L Baillie; Angel Balmaseda; Alfredo Barahona; Sudha Basnet; Quique Bassat; Wilma Basualdo; Godfrey Bigogo; Louis Bont; Robert F Breiman; W Abdullah Brooks; Shobha Broor; Nigel Bruce; Dana Bruden; Philippe Buchy; Stuart Campbell; Phyllis Carosone-Link; Mandeep Chadha; James Chipeta; Monidarin Chou; Wilfrido Clara; Cheryl Cohen; Elizabeth de Cuellar; Duc-Anh Dang; Budragchaagiin Dash-Yandag; Maria Deloria-Knoll; Mukesh Dherani; Tekchheng Eap; Bernard E Ebruke; Marcela Echavarria; Carla Cecília de Freitas Lázaro Emediato; Rodrigo A Fasce; Daniel R Feikin; Luzhao Feng; Angela Gentile; Aubree Gordon; Doli Goswami; Sophie Goyet; Michelle Groome; Natasha Halasa; Siddhivinayak Hirve; Nusrat Homaira; Stephen R C Howie; Jorge Jara; Imane Jroundi; Cissy B Kartasasmita; Najwa Khuri-Bulos; Karen L Kotloff; Anand Krishnan; Romina Libster; Olga Lopez; Marilla G Lucero; Florencia Lucion; Socorro P Lupisan; Debora N Marcone; John P McCracken; Mario Mejia; Jennifer C Moisi; Joel M Montgomery; David P Moore; Cinta Moraleda; Jocelyn Moyes; Patrick Munywoki; Kuswandewi Mutyara; Mark P Nicol; D James Nokes; Pagbajabyn Nymadawa; Maria Tereza da Costa Oliveira; Histoshi Oshitani; Nitin Pandey; Gláucia Paranhos-Baccalà; Lia N Phillips; Valentina Sanchez Picot; Mustafizur Rahman; Mala Rakoto-Andrianarivelo; Zeba A Rasmussen; Barbara A Rath; Annick Robinson; Candice Romero; Graciela Russomando; Vahid Salimi; Pongpun Sawatwong; Nienke Scheltema; Brunhilde Schweiger; J Anthony G Scott; Phil Seidenberg; Kunling Shen; Rosalyn Singleton; Viviana Sotomayor; Tor A Strand; Agustinus Sutanto; Mariam Sylla; Milagritos D Tapia; Somsak Thamthitiwat; Elizabeth D Thomas; Rafal Tokarz; Claudia Turner; Marietjie Venter; Sunthareeya Waicharoen; Jianwei Wang; Wanitda Watthanaworawit; Lay-Myint Yoshida; Hongjie Yu; Heather J Zar; Harry Campbell; Harish Nair Journal: Lancet Date: 2017-07-07 Impact factor: 79.321
Authors: Elizabeth J McFarland; Ruth A Karron; Petronella Muresan; Coleen K Cunningham; Charlotte Perlowski; Jennifer Libous; Jennifer Oliva; Patrick Jean-Philippe; Jack Moye; Elizabeth Schappell; Emily Barr; Vivian Rexroad; Laura Fearn; Mikhaela Cielo; Andrew Wiznia; Jaime G Deville; Lijuan Yang; Cindy Luongo; Peter L Collins; Ursula J Buchholz Journal: J Infect Dis Date: 2020-06-11 Impact factor: 5.226
Authors: Jeremy V Camp; Robert L Wilson; Morgan Singletary; James L Blanchard; Anna Aldovini; Robert W Kaminski; Edwin V Oaks; Pamela A Kozlowski Journal: Vaccine X Date: 2021-06-24
Authors: Catalina A Andrade; Gaspar A Pacheco; Nicolas M S Gálvez; Jorge A Soto; Susan M Bueno; Alexis M Kalergis Journal: Viruses Date: 2020-06-12 Impact factor: 5.048