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Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001

Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001
Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001

Objectives: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. Methods: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. Results: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18–55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. Conclusions: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.

Adjuvanted vaccine, COVID-19, Coronavirus, CpG 1018, Inactivated vaccine, Neutralizing antibody, RBD-binding IgG antibody, S protein binding IgG antibody, SARS-CoV-2, Whole-virus vaccine
0163-4453
306 - 317
Lazarus, Rajeka
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Taucher, Christian
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Brown, Claire
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Corbic, Irena
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Danon, Leon
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Dubischar, Katrin
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Duncan, Christopher J A
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Eder-Lingelbach, Susanne
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Faust, Saul N
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Green, Christopher
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Gokani, Karishma
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Hochreiter, Romana
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Wright, Johanna Kellett
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Kwon, Dowan
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Middleditch, Alexander
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Munro, Alasdair P S
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Naker, Kush
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Penciu, Florentina
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Price, David
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Querton, Benedicte
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Riaz, Tawassal
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Ross-Russell, Amy
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Sanchez-Gonzalez, Amada
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Wardle, Hayley
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Warren, Sarah
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Finn, Adam
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et al.
Valneva Phase 1 Trial Group
Lazarus, Rajeka
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Taucher, Christian
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Brown, Claire
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Corbic, Irena
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Danon, Leon
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Dubischar, Katrin
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Duncan, Christopher J A
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Eder-Lingelbach, Susanne
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Faust, Saul N
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Green, Christopher
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Gokani, Karishma
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Hochreiter, Romana
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Wright, Johanna Kellett
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Kwon, Dowan
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Middleditch, Alexander
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Munro, Alasdair P S
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Naker, Kush
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Penciu, Florentina
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Price, David
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Querton, Benedicte
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Riaz, Tawassal
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Ross-Russell, Amy
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Sanchez-Gonzalez, Amada
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Wardle, Hayley
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Warren, Sarah
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Finn, Adam
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Lazarus, Rajeka, Taucher, Christian, Brown, Claire, Corbic, Irena, Danon, Leon and Dubischar, Katrin , et al. and Valneva Phase 1 Trial Group (2022) Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001. Journal of Infection, 85 (3), 306 - 317. (doi:10.1016/j.jinf.2022.06.009).

Record type: Article

Abstract

Objectives: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. Methods: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. Results: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18–55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. Conclusions: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.

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Accepted/In Press date: 11 June 2022
e-pub ahead of print date: 16 June 2022
Published date: September 2022
Additional Information: Funding Information: This study has been funded by the Department of Health and Social Care, UK; and by Valneva Austria GmbH. The authors would like to thank the National Institute for Health and Care Research (NIHR) for recruitment support. The authors are grateful to the European Medicines Agency (EMA, UK Medicines and Healthcare products Regulatory Agency (MHRA) and Health Research Authority (HRA) for their extraordinary efforts in rapidly reviewing submissions, for their attention to detail and input into trial design. This report is independent research paid for by the Department of Health and Social Care. Theviews expressed in this publication are those of the author(s) and not necessarily those of the Department of Health and Social Care. The authors express their gratitude for the contribution of all trial participants, and theinvaluable advice of the trial committees. Heinz Burgmann, Tom Wilkinson, Martin Sauer, Hermann Laferl and Eva Poellabauer served as the independent members of the data and safety monitoring committee. The views expressed in this publication are those of the author(s) and not necessarily those of their employers or funders. Publisher Copyright: © 2022
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Keywords: Adjuvanted vaccine, COVID-19, Coronavirus, CpG 1018, Inactivated vaccine, Neutralizing antibody, RBD-binding IgG antibody, S protein binding IgG antibody, SARS-CoV-2, Whole-virus vaccine
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Identifiers

Local EPrints ID: 468246
URI: http://eprints.soton.ac.uk/id/eprint/468246
DOI: doi:10.1016/j.jinf.2022.06.009
ISSN: 0163-4453
PURE UUID: cdd9dbc8-a815-4bb8-afe8-0e108925e13b
ORCID for Saul N Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Alasdair P S Munro: ORCID iD orcid.org/0000-0002-4317-0742

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Date deposited: 08 Aug 2022 16:53
Last modified: 23 Nov 2024 03:00

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Contributors

Author: Rajeka Lazarus
Author: Christian Taucher
Author: Claire Brown
Author: Irena Corbic
Author: Leon Danon
Author: Katrin Dubischar
Author: Christopher J A Duncan
Author: Susanne Eder-Lingelbach
Author: Saul N Faust ORCID iD
Author: Christopher Green
Author: Karishma Gokani
Author: Romana Hochreiter
Author: Johanna Kellett Wright
Author: Dowan Kwon
Author: Alexander Middleditch
Author: Alasdair P S Munro ORCID iD
Author: Kush Naker
Author: Florentina Penciu
Author: David Price
Author: Benedicte Querton
Author: Tawassal Riaz
Author: Amy Ross-Russell
Author: Amada Sanchez-Gonzalez
Author: Hayley Wardle
Author: Sarah Warren
Author: Adam Finn
Corporate Author: et al.
Corporate Author: Valneva Phase 1 Trial Group

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