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

Valneva Phase 1 Trial Group, Rajeka Lazarus, Christian Taucher*, Claire Brown, Irena Čorbic Ramljak, Leon Danon, Katrin Dubischar, Christopher J. A. Duncan, Susanne Eder-Lingelbach, Saul N. Faust, Christopher Green, Karishma Gokani, Romana Hochreiter, Johanna Kellett Wright, Dowan Kwon, Alex Middleditch, Alasdair P.S. Munro, Kush Naker, Florentina Penciu, David PriceBenedicte Querton, Tawassal Riaz, Amy Ross-Russell, Amada Sanchez-Gonzalez, Hayley Wardle, Sarah Warren, Adam Finn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)306-317
Number of pages12
JournalJournal of Infection
Volume85
Issue number3
Early online date16 Jun 2022
DOIs
Publication statusPublished - Sept 2022

Bibliographical note

Funding:
This study has been funded by the Department of Health and Social Care, UK; and by Valneva Austria GmbH.

Keywords

  • Coronavirus
  • SARS-CoV-2
  • COVID-19
  • Whole-virus vaccine
  • Inactivated vaccine
  • Adjuvanted vaccine
  • Neutralizing antibody
  • S protein binding IgG antibody
  • RBD-binding IgG antibody
  • CpG 1018

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