Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: a randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults.
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.
Author
Lazarus, Rajeka
Taucher, Christian
Brown, Claire
Čorbic Ramljak, Irena
Danon, Leon
Dubischar, Katrin
Duncan, Christopher J A
Eder-Lingelbach, Susanne
Faust, Saul N
Green, Christopher
Gokani, Karishma
Hochreiter, Romana
Wright, Johanna Kellett
Kwon, Dowan
Middleditch, Alexander
Munro, Alasdair P S
Naker, Kush
Penciu, Florentina
Price, David
Querton, Benedicte
Riaz, Tawassal
Ross-Russell, Amy
Sanchez-Gonzalez, Amada
Wardle, Hayley
Warren, Sarah
Finn, Adam
Taucher, Christian
Brown, Claire
Čorbic Ramljak, Irena
Danon, Leon
Dubischar, Katrin
Duncan, Christopher J A
Eder-Lingelbach, Susanne
Faust, Saul N
Green, Christopher
Gokani, Karishma
Hochreiter, Romana
Wright, Johanna Kellett
Kwon, Dowan
Middleditch, Alexander
Munro, Alasdair P S
Naker, Kush
Penciu, Florentina
Price, David
Querton, Benedicte
Riaz, Tawassal
Ross-Russell, Amy
Sanchez-Gonzalez, Amada
Wardle, Hayley
Warren, Sarah
Finn, Adam
Citations
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Date
2022-06-16
Type
Article
Subject
Communicable diseases, Microbiology. Immunology
Collections
Citation
Lazarus R, Taucher C, Brown C, Čorbic Ramljak I, Danon L, Dubischar K, Duncan CJA, Eder-Lingelbach S, Faust SN, Green C, Gokani K, Hochreiter R, Wright JK, Kwon D, Middleditch A, Munro APS, Naker K, Penciu F, Price D, Querton B, Riaz T, Ross-Russell A, Sanchez-Gonzalez A, Wardle H, Warren S, Finn A; Valneva Phase 1 Trial Group. Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults. J Infect. 2022 Sep;85(3):306-317. doi: 10.1016/j.jinf.2022.06.009. Epub 2022 Jun 16
Journal / Source Title
Journal of Infection
DOI
10.1016/j.jinf.2022.06.009
PMID
35718205
Publisher
Elsevier
Publisher’s URL
http://www.sciencedirect.com/science/journal/01634453