Immunogenicity and tolerability of a bivalent virus-like particle norovirus vaccine candidate in children from 6 months up to 4 years of age : A phase 2 randomized, double-blind trial
We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6-≤12 months and 1-≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6-≤12-month-old groups, but less so in the 1-≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Human vaccines & immunotherapeutics - 19(2023), 1 vom: 31. Dez., Seite 2204787 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
López, Pio [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.06.2023 Date Revised 01.07.2023 published: Print-Electronic ClinicalTrials.gov: NCT02153112 Citation Status MEDLINE |
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| doi: |
10.1080/21645515.2023.2204787 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356438325 |
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| 100 | 1 | |a López, Pio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Immunogenicity and tolerability of a bivalent virus-like particle norovirus vaccine candidate in children from 6 months up to 4 years of age |b A phase 2 randomized, double-blind trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 28.06.2023 | ||
| 500 | |a Date Revised 01.07.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02153112 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6-≤12 months and 1-≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3. On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6-≤12-month-old groups, but less so in the 1-≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Norovirus | |
| 650 | 4 | |a children | |
| 650 | 4 | |a immunogenicity | |
| 650 | 4 | |a reactogenicity | |
| 650 | 4 | |a vaccine | |
| 650 | 4 | |a virus-like particles | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Vaccines, Virus-Like Particle |2 NLM | |
| 700 | 1 | |a López-Medina, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Sáez-Llorens, Xavier |e verfasserin |4 aut | |
| 700 | 1 | |a deAntonio, Rodrigo |e verfasserin |4 aut | |
| 700 | 1 | |a Masuda, Taisei |e verfasserin |4 aut | |
| 700 | 1 | |a Mendelman, Paul M |e verfasserin |4 aut | |
| 700 | 1 | |a Sherwood, James |e verfasserin |4 aut | |
| 700 | 1 | |a Baehner, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Borkowski, Astrid |e verfasserin |4 aut | |
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