Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial.
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| Title: | Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial. |
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| Authors: | Tschismarov, Roland (AUTHOR), Van Damme, Pierre (AUTHOR), Germain, Clara (AUTHOR), De Coster, Ilse (AUTHOR), Mateo, Mathieu (AUTHOR), Reynard, Stephanie (AUTHOR), Journeaux, Alexandra (AUTHOR), Tomberger, Yvonne (AUTHOR), Withanage, Kanchanamala (AUTHOR), Haslwanter, Denise (AUTHOR), Terler, Katherine (AUTHOR), Schrauf, Sabrina (AUTHOR), Müllner, Matthias (AUTHOR), Tauber, Erich (AUTHOR), Ramsauer, Katrin (AUTHOR), Baize, Sylvain (AUTHOR) |
| Source: | Lancet. Apr2023, Vol. 401 Issue 10384, p1267-1276. 10p. |
| Subjects: | Lassa fever, Immune response, Tissue culture, Databases, Vaccines |
| Geographic Terms: | Antwerp (Belgium) |
| Abstract: | Lassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV). This first-in-human phase 1 trial—consisting of an open-label dose-escalation stage and an observer-blinded, randomised, placebo-controlled treatment stage—was conducted at a single site at the University of Antwerp, Antwerp, Belgium, and involved healthy adults aged 18–55 years. Participants in the dose-escalation stage were sequentially assigned to a low-dose group (two intramuscular doses of MV-LASV at 2 × 104 times the median tissue culture infectious dose) or a high-dose group (two doses at 1 × 105 times the median tissue culture infectious dose). Participants in the double-blinded treatment stage were randomly assigned in a 2:2:1 ratio to receive low dose, high dose, or placebo. The primary endpoint was the rate of solicited and unsolicited adverse events up to study day 56 and was assessed in all participants who received at least one dose of investigational product. The trial is registered with ClinicalTrials.gov , NCT04055454 , and the European Union Drug Regulating Authorities Clinical Trials Database, 2018-003647-40, and is complete. Between Sept 26, 2019, and Jan 20, 2020, 60 participants were enrolled and assigned to receive placebo (n=12) or MV-LASV (n=48). All 60 participants received at least one study treatment. Most adverse events occurred during the treatment phase, and frequencies of total solicited or unsolicited adverse events were similar between treatment groups, with 96% of participants in the low-dose group, 100% of those in the high-dose group, and 92% of those in the placebo group having any solicited adverse event (p=0·6751) and 76% of those in the low-dose group, 70% of those in the high-dose group, and 100% of those in the placebo group having any unsolicited adverse event (p=0·1047). The only significant difference related to local solicited adverse events, with higher frequencies observed in groups receiving MV-LASV (24 [96%] of 25 participants in the low-dose group; all 23 [100%] participants in the high-dose group) than in the placebo group (6 [50%] of 12 participants; p=0·0001, Fisher-Freeman-Halton test). Adverse events were mostly of mild or moderate severity, and no serious adverse events were observed. MV-LASV also induced substantial concentrations of LASV-specific IgG (geometric mean titre 62·9 EU/ml in the low-dose group and 145·9 EU/ml in the high-dose group on day 42). MV-LASV showed an acceptable safety and tolerability profile, and immunogenicity seemed to be unaffected by pre-existing immunity against the vector. MV-LASV is therefore a promising candidate for further development. Coalition for Epidemic Preparedness Innovations. [ABSTRACT FROM AUTHOR] |
| Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 163087665 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Tschismarov%2C+Roland%22">Tschismarov, Roland</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Van+Damme%2C+Pierre%22">Van Damme, Pierre</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Germain%2C+Clara%22">Germain, Clara</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22De+Coster%2C+Ilse%22">De Coster, Ilse</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mateo%2C+Mathieu%22">Mateo, Mathieu</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Reynard%2C+Stephanie%22">Reynard, Stephanie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Journeaux%2C+Alexandra%22">Journeaux, Alexandra</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tomberger%2C+Yvonne%22">Tomberger, Yvonne</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Withanage%2C+Kanchanamala%22">Withanage, Kanchanamala</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Haslwanter%2C+Denise%22">Haslwanter, Denise</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Terler%2C+Katherine%22">Terler, Katherine</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Schrauf%2C+Sabrina%22">Schrauf, Sabrina</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Müllner%2C+Matthias%22">Müllner, Matthias</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tauber%2C+Erich%22">Tauber, Erich</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ramsauer%2C+Katrin%22">Ramsauer, Katrin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Baize%2C+Sylvain%22">Baize, Sylvain</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. Apr2023, Vol. 401 Issue 10384, p1267-1276. 10p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Lassa+fever%22">Lassa fever</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+response%22">Immune response</searchLink><br /><searchLink fieldCode="DE" term="%22Tissue+culture%22">Tissue culture</searchLink><br /><searchLink fieldCode="DE" term="%22Databases%22">Databases</searchLink><br /><searchLink fieldCode="DE" term="%22Vaccines%22">Vaccines</searchLink> – Name: SubjectGeographic Label: Geographic Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Antwerp+%28Belgium%29%22">Antwerp (Belgium)</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Lassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV). This first-in-human phase 1 trial—consisting of an open-label dose-escalation stage and an observer-blinded, randomised, placebo-controlled treatment stage—was conducted at a single site at the University of Antwerp, Antwerp, Belgium, and involved healthy adults aged 18–55 years. Participants in the dose-escalation stage were sequentially assigned to a low-dose group (two intramuscular doses of MV-LASV at 2 × 104 times the median tissue culture infectious dose) or a high-dose group (two doses at 1 × 105 times the median tissue culture infectious dose). Participants in the double-blinded treatment stage were randomly assigned in a 2:2:1 ratio to receive low dose, high dose, or placebo. The primary endpoint was the rate of solicited and unsolicited adverse events up to study day 56 and was assessed in all participants who received at least one dose of investigational product. The trial is registered with ClinicalTrials.gov , NCT04055454 , and the European Union Drug Regulating Authorities Clinical Trials Database, 2018-003647-40, and is complete. Between Sept 26, 2019, and Jan 20, 2020, 60 participants were enrolled and assigned to receive placebo (n=12) or MV-LASV (n=48). All 60 participants received at least one study treatment. Most adverse events occurred during the treatment phase, and frequencies of total solicited or unsolicited adverse events were similar between treatment groups, with 96% of participants in the low-dose group, 100% of those in the high-dose group, and 92% of those in the placebo group having any solicited adverse event (p=0·6751) and 76% of those in the low-dose group, 70% of those in the high-dose group, and 100% of those in the placebo group having any unsolicited adverse event (p=0·1047). The only significant difference related to local solicited adverse events, with higher frequencies observed in groups receiving MV-LASV (24 [96%] of 25 participants in the low-dose group; all 23 [100%] participants in the high-dose group) than in the placebo group (6 [50%] of 12 participants; p=0·0001, Fisher-Freeman-Halton test). Adverse events were mostly of mild or moderate severity, and no serious adverse events were observed. MV-LASV also induced substantial concentrations of LASV-specific IgG (geometric mean titre 62·9 EU/ml in the low-dose group and 145·9 EU/ml in the high-dose group on day 42). MV-LASV showed an acceptable safety and tolerability profile, and immunogenicity seemed to be unaffected by pre-existing immunity against the vector. MV-LASV is therefore a promising candidate for further development. Coalition for Epidemic Preparedness Innovations. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(23)00048-X Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 1267 Subjects: – SubjectFull: Lassa fever Type: general – SubjectFull: Immune response Type: general – SubjectFull: Tissue culture Type: general – SubjectFull: Databases Type: general – SubjectFull: Vaccines Type: general – SubjectFull: Antwerp (Belgium) Type: general Titles: – TitleFull: Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Tschismarov, Roland – PersonEntity: Name: NameFull: Van Damme, Pierre – PersonEntity: Name: NameFull: Germain, Clara – PersonEntity: Name: NameFull: De Coster, Ilse – PersonEntity: Name: NameFull: Mateo, Mathieu – PersonEntity: Name: NameFull: Reynard, Stephanie – PersonEntity: Name: NameFull: Journeaux, Alexandra – PersonEntity: Name: NameFull: Tomberger, Yvonne – PersonEntity: Name: NameFull: Withanage, Kanchanamala – PersonEntity: Name: NameFull: Haslwanter, Denise – PersonEntity: Name: NameFull: Terler, Katherine – PersonEntity: Name: NameFull: Schrauf, Sabrina – PersonEntity: Name: NameFull: Müllner, Matthias – PersonEntity: Name: NameFull: Tauber, Erich – PersonEntity: Name: NameFull: Ramsauer, Katrin – PersonEntity: Name: NameFull: Baize, Sylvain IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 04 Text: Apr2023 Type: published Y: 2023 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 401 – Type: issue Value: 10384 Titles: – TitleFull: Lancet Type: main |
| ResultId | 1 |
