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 Price; Benedicte Querton; Tawassal Riaz; Amy Ross-Russell; Amada Sanchez-Gonzalez; Hayley Wardle; Sarah Warren; Adam Finn

doi:10.1016/j.jinf.2022.06.009

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

Chemical Engineering

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	306-317
Number of pages	12
Journal	Journal of Infection
Volume	85
Issue number	3
Early online date	16 Jun 2022
DOIs	https://doi.org/10.1016/j.jinf.2022.06.009
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jinf.2022.06.009

https://research-information.bris.ac.uk/en/publications/safety-and-immunogenicity-of-the-inactivated-whole-virus-adjuvant

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Valneva Phase 1 Trial Group, Lazarus, R., Taucher, C., Brown, C., Ramljak, I. Č., Danon, L., Dubischar, K., Duncan, C. J. A., Eder-Lingelbach, S., Faust, S. N., Green, C., Gokani, K., Hochreiter, R., Wright, J. K., Kwon, D., Middleditch, A., Munro, A. P. S., Naker, K., Penciu, F., ... Finn, A. (2022). 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. Journal of Infection, 85(3), 306-317. https://doi.org/10.1016/j.jinf.2022.06.009

@article{d2a5b6e4dfff4a26bafd08890c9db097,

title = "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.",

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",

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

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

year = "2022",

month = sep,

doi = "10.1016/j.jinf.2022.06.009",

language = "English",

volume = "85",

pages = "306--317",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "Elsevier",

number = "3",

}

Valneva Phase 1 Trial Group, Lazarus, R, Taucher, C, Brown, C, Ramljak, IČ, 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 2022, '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', Journal of Infection, vol. 85, no. 3, pp. 306-317. https://doi.org/10.1016/j.jinf.2022.06.009

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; Lazarus, Rajeka; Taucher, Christian et al.
In: Journal of Infection, Vol. 85, No. 3, 09.2022, p. 306-317.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001

T2 - A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults

AU - Valneva Phase 1 Trial Group

AU - Lazarus, Rajeka

AU - Taucher, Christian

AU - Brown, Claire

AU - Ramljak, Irena Čorbic

AU - Danon, Leon

AU - Dubischar, Katrin

AU - Duncan, Christopher J. A.

AU - Eder-Lingelbach, Susanne

AU - Faust, Saul N.

AU - Green, Christopher

AU - Gokani, Karishma

AU - Hochreiter, Romana

AU - Wright, Johanna Kellett

AU - Kwon, Dowan

AU - Middleditch, Alex

AU - Munro, Alasdair P.S.

AU - Naker, Kush

AU - Penciu, Florentina

AU - Price, David

AU - Querton, Benedicte

AU - Riaz, Tawassal

AU - Ross-Russell, Amy

AU - Sanchez-Gonzalez, Amada

AU - Wardle, Hayley

AU - Warren, Sarah

AU - Finn, Adam

N1 - Funding: This study has been funded by the Department of Health and Social Care, UK; and by Valneva Austria GmbH.

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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.

KW - Coronavirus

KW - SARS-CoV-2

KW - COVID-19

KW - Whole-virus vaccine

KW - Inactivated vaccine

KW - Adjuvanted vaccine

KW - Neutralizing antibody

KW - S protein binding IgG antibody

KW - RBD-binding IgG antibody

KW - CpG 1018

U2 - 10.1016/j.jinf.2022.06.009

DO - 10.1016/j.jinf.2022.06.009

M3 - Article

SN - 0163-4453

VL - 85

SP - 306

EP - 317

JO - Journal of Infection

JF - Journal of Infection

IS - 3

ER -

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

Bibliographical note

Keywords

UN SDGs

Access to Document

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