Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine
Background: V-306 is a virus-like particle-based vaccine candidate displaying respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm) as an antigenic epitope. Methods: This was a randomized, placebo-controlled, double-blind, dose-escalating, first-in-human study, conducted in 60 women a...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/11/2/367 |
| _version_ | 1797617880670404608 |
|---|---|
| author | Isabel Leroux-Roels Jacques Bruhwyler Lilli Stergiou Mark Sumeray Jasper Joye Cathy Maes Paul-Henri Lambert Geert Leroux-Roels |
| author_facet | Isabel Leroux-Roels Jacques Bruhwyler Lilli Stergiou Mark Sumeray Jasper Joye Cathy Maes Paul-Henri Lambert Geert Leroux-Roels |
| author_sort | Isabel Leroux-Roels |
| collection | DOAJ |
| description | Background: V-306 is a virus-like particle-based vaccine candidate displaying respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm) as an antigenic epitope. Methods: This was a randomized, placebo-controlled, double-blind, dose-escalating, first-in-human study, conducted in 60 women aged 18–45 years. Twenty subjects per cohort (15 vaccine and five placebo) received two V-306 intramuscular administrations on Days 0 and 56 at 15 µg, 50 µg, or 150 µg. Safety and immunogenicity were assessed after each vaccination and for 1 year in total. Results: V-306 was safe and well tolerated at all dose levels, with no increase in reactogenicity and unsolicited adverse events between the first and second administrations. At 50 µg and 150 µg, V-306 induced an increase in FsIIm-specific immunoglobulin G (IgG) titers, which lasted at least 4 months. This did not translate into an increase in RSV-neutralizing antibody titers, which were already high at baseline. No increase in the anti-F protein-specific IgG titers was observed, which were also high in most subjects at baseline due to past natural infections. Conclusions: V-306 was safe and well-tolerated. Future modifications of the vaccine and assay conditions will likely improve the results of vaccination. |
| first_indexed | 2024-03-11T08:02:14Z |
| format | Article |
| id | doaj.art-d1f8627e0ae3494790e5e9ab8ef65d00 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T08:02:14Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d1f8627e0ae3494790e5e9ab8ef65d002023-11-16T23:43:26ZengMDPI AGVaccines2076-393X2023-02-0111236710.3390/vaccines11020367Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV VaccineIsabel Leroux-Roels0Jacques Bruhwyler1Lilli Stergiou2Mark Sumeray3Jasper Joye4Cathy Maes5Paul-Henri Lambert6Geert Leroux-Roels7Center for Vaccinology (CEVAC), Ghent University Hospital, Corneel Heymanslaan 10, B-9000 Ghent, BelgiumExpert Clinical Services Organization (ECSOR) sa/nv, Rue de la Station 78, B-1630 Linkebeek, BelgiumVirometix AG, Wagistrasse 14, 8952 Schlieren, SwitzerlandVirometix AG, Wagistrasse 14, 8952 Schlieren, SwitzerlandCenter for Vaccinology (CEVAC), Ghent University Hospital, Corneel Heymanslaan 10, B-9000 Ghent, BelgiumCenter for Vaccinology (CEVAC), Ghent University Hospital, Corneel Heymanslaan 10, B-9000 Ghent, BelgiumDepartment of Paediatrics, Gynecology and Obstetrics, University of Geneva, Rue du Général Dufour 24, 1211 Geneva, SwitzerlandCenter for Vaccinology (CEVAC), Ghent University Hospital, Corneel Heymanslaan 10, B-9000 Ghent, BelgiumBackground: V-306 is a virus-like particle-based vaccine candidate displaying respiratory syncytial virus (RSV) F site II protein mimetics (FsIIm) as an antigenic epitope. Methods: This was a randomized, placebo-controlled, double-blind, dose-escalating, first-in-human study, conducted in 60 women aged 18–45 years. Twenty subjects per cohort (15 vaccine and five placebo) received two V-306 intramuscular administrations on Days 0 and 56 at 15 µg, 50 µg, or 150 µg. Safety and immunogenicity were assessed after each vaccination and for 1 year in total. Results: V-306 was safe and well tolerated at all dose levels, with no increase in reactogenicity and unsolicited adverse events between the first and second administrations. At 50 µg and 150 µg, V-306 induced an increase in FsIIm-specific immunoglobulin G (IgG) titers, which lasted at least 4 months. This did not translate into an increase in RSV-neutralizing antibody titers, which were already high at baseline. No increase in the anti-F protein-specific IgG titers was observed, which were also high in most subjects at baseline due to past natural infections. Conclusions: V-306 was safe and well-tolerated. Future modifications of the vaccine and assay conditions will likely improve the results of vaccination.https://www.mdpi.com/2076-393X/11/2/367respiratory syncytial virusRSVvaccinephase Ihealthy volunteerssafety |
| spellingShingle | Isabel Leroux-Roels Jacques Bruhwyler Lilli Stergiou Mark Sumeray Jasper Joye Cathy Maes Paul-Henri Lambert Geert Leroux-Roels Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine Vaccines respiratory syncytial virus RSV vaccine phase I healthy volunteers safety |
| title | Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine |
| title_full | Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine |
| title_fullStr | Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine |
| title_full_unstemmed | Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine |
| title_short | Double-Blind, Placebo-Controlled, Dose-Escalating Study Evaluating the Safety and Immunogenicity of an Epitope-Specific Chemically Defined Nanoparticle RSV Vaccine |
| title_sort | double blind placebo controlled dose escalating study evaluating the safety and immunogenicity of an epitope specific chemically defined nanoparticle rsv vaccine |
| topic | respiratory syncytial virus RSV vaccine phase I healthy volunteers safety |
| url | https://www.mdpi.com/2076-393X/11/2/367 |
| work_keys_str_mv | AT isabellerouxroels doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT jacquesbruhwyler doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT lillistergiou doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT marksumeray doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT jasperjoye doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT cathymaes doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT paulhenrilambert doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine AT geertlerouxroels doubleblindplacebocontrolleddoseescalatingstudyevaluatingthesafetyandimmunogenicityofanepitopespecificchemicallydefinednanoparticlersvvaccine |