Background: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing the F-, N- and M2-1 proteins, administered to 12-23-month-old RSV-seropositive children followed for 2 years post-vaccination. Methods: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (1:1) (Day 1 and 31). Doses escalated from 0.5 × 1010 low (LD) to 1.5 × 1010 medium (MD) to 5 × 1010 high (HD) viral particles after safety assessment. Study endpoints included anti-RSV-A neutralizing antibody (Nab) titers through Year 1, and safety through Year 2. Results: Eighty-two participants were vaccinated: 11 RSV-LD, 14 RSV-MD, 18 RSV-HD, 39 placebo. Solicited adverse events were similar across groups, except fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups post-dose 1 without further increase post-dose 2. RSV-A Nab titers remained higher than pre-vaccination levels at Year 1. Conclusions: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed post-dose 1 with no observed booster effect post-dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. Trial registration: clinicaltrials.gov NCT02927873, URL: https://www.clinicaltrials.gov/ct2/show/NCT02927873.

Safety and immunogenicity of a ChAd155-vectored RSV vaccine (ChAd155-RSV) in healthy RSV-seropositive children 12-23 months of age / Díez-Domingo, Javier; Sáez-Llorens, Xavier; Rodriguez-Weber, Miguel A; Epalza, Cristina; Chatterjee, Archana; Chiu, Cheng-Hsun; Lin, Chien-Yu; Berry, Andrea A; Martinón-Torres, Federico; Baquero-Artigao, Fernando; Langley, Joanne M; Ramos Amador, José T; Domachowske, Joseph B; Huang, Li-Min; Chiu, Nan-Chang; Esposito, Susanna; Moris, Philippe; Nguyen, Thi Lien-Anh; Nikic, Vanja; Woo, Wayne; Zhou, Yingjun; Dieussaert, Ilse; Leach, Amanda; Gonzalez Lopez, Antonio; Vanhoutte, Nicolas. - In: THE JOURNAL OF INFECTIOUS DISEASES. - ISSN 0022-1899. - (2022). [10.1093/infdis/jiac481]

Safety and immunogenicity of a ChAd155-vectored RSV vaccine (ChAd155-RSV) in healthy RSV-seropositive children 12-23 months of age

Esposito, Susanna;Gonzalez Lopez, Antonio;
2022-01-01

Abstract

Background: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing the F-, N- and M2-1 proteins, administered to 12-23-month-old RSV-seropositive children followed for 2 years post-vaccination. Methods: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (1:1) (Day 1 and 31). Doses escalated from 0.5 × 1010 low (LD) to 1.5 × 1010 medium (MD) to 5 × 1010 high (HD) viral particles after safety assessment. Study endpoints included anti-RSV-A neutralizing antibody (Nab) titers through Year 1, and safety through Year 2. Results: Eighty-two participants were vaccinated: 11 RSV-LD, 14 RSV-MD, 18 RSV-HD, 39 placebo. Solicited adverse events were similar across groups, except fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups post-dose 1 without further increase post-dose 2. RSV-A Nab titers remained higher than pre-vaccination levels at Year 1. Conclusions: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed post-dose 1 with no observed booster effect post-dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. Trial registration: clinicaltrials.gov NCT02927873, URL: https://www.clinicaltrials.gov/ct2/show/NCT02927873.
2022
Safety and immunogenicity of a ChAd155-vectored RSV vaccine (ChAd155-RSV) in healthy RSV-seropositive children 12-23 months of age / Díez-Domingo, Javier; Sáez-Llorens, Xavier; Rodriguez-Weber, Miguel A; Epalza, Cristina; Chatterjee, Archana; Chiu, Cheng-Hsun; Lin, Chien-Yu; Berry, Andrea A; Martinón-Torres, Federico; Baquero-Artigao, Fernando; Langley, Joanne M; Ramos Amador, José T; Domachowske, Joseph B; Huang, Li-Min; Chiu, Nan-Chang; Esposito, Susanna; Moris, Philippe; Nguyen, Thi Lien-Anh; Nikic, Vanja; Woo, Wayne; Zhou, Yingjun; Dieussaert, Ilse; Leach, Amanda; Gonzalez Lopez, Antonio; Vanhoutte, Nicolas. - In: THE JOURNAL OF INFECTIOUS DISEASES. - ISSN 0022-1899. - (2022). [10.1093/infdis/jiac481]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2936722
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