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

Rajeka Lazarus; Christian Taucher; Claire Brown; Irena Čorbic Ramljak; Leon Danon; Katrin Dubischar; Christopher J.A. Duncan; Johanna Kellett Wright; Dowan Kwon; Alexander Middleditch; Florentina Penciu; Tawassal Riaz; Adam Finn; Valneva Phase 1 Trial Group

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

Rajeka Lazarus, Christian Taucher^*, Claire Brown, Irena Čorbic Ramljak, Leon Danon, Katrin Dubischar, Christopher J.A. Duncan, Johanna Kellett Wright, Dowan Kwon, Alexander Middleditch, Florentina Penciu, Tawassal Riaz, Adam Finn, Valneva Phase 1 Trial Group

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

16 Citations (Scopus)

58 Downloads (Pure)

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	15 Jun 2022
DOIs	https://doi.org/10.1016/j.jinf.2022.06.009
Publication status	Published - 1 Sept 2022

Bibliographical note

Publisher Copyright:
© 2022 Published by Elsevier Ltd on behalf of The British Infection Association.

Research Groups and Themes

Covid19

Keywords

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

UN SDGs

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

Access to Document

10.1016/j.jinf.2022.06.009

Full-text PDF (accepted author manuscript)
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier athttps://doi.org/10.1016/j.jinf.2022.06.009. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 1.25 MBLicence: CC BY-NC-ND

Handle.net

Persistent link

Cite this

Lazarus, R., Taucher, C., Brown, C., Čorbic Ramljak, I., Danon, L., Dubischar, K., Duncan, C. J. A., Wright, J. K., Kwon, D., Middleditch, A., Penciu, F., Riaz, T., Finn, A., & Valneva Phase 1 Trial Group (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{510a38f68fda4f39a422085b50717b8e,

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

author = "Rajeka Lazarus and Christian Taucher and Claire Brown and {{\v C}orbic Ramljak}, Irena 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 Alexander 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 and {Valneva Phase 1 Trial Group}",

note = "Publisher Copyright: {\textcopyright} 2022 Published by Elsevier Ltd on behalf of The British Infection Association.",

year = "2022",

month = sep,

day = "1",

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

language = "English",

volume = "85",

pages = "306--317",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders",

number = "3",

}

Lazarus, R, Taucher, C, Brown, C, Čorbic Ramljak, I, Danon, L, Dubischar, K, Duncan, CJA, Wright, JK, Kwon, D, Middleditch, A, Penciu, F, Riaz, T, Finn, A & Valneva Phase 1 Trial Group 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. / Lazarus, Rajeka; Taucher, Christian; Brown, Claire et al.
In: Journal of Infection, Vol. 85, No. 3, 01.09.2022, p. 306-317.

Research output: Contribution to journal › Article (Academic Journal) › 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 - Lazarus, Rajeka

AU - Taucher, Christian

AU - Brown, Claire

AU - Čorbic Ramljak, Irena

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, Alexander

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

AU - Valneva Phase 1 Trial Group

PY - 2022/9/1

Y1 - 2022/9/1

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 - Adjuvanted vaccine

KW - Coronavirus

KW - COVID-19

KW - CpG 1018

KW - Inactivated vaccine

KW - Neutralizing antibody

KW - RBD-binding IgG antibody

KW - S protein binding IgG antibody

KW - SARS-CoV-2

KW - Whole-virus vaccine

U2 - 10.1016/j.jinf.2022.06.009

DO - 10.1016/j.jinf.2022.06.009

M3 - Article (Academic Journal)

C2 - 35718205

AN - SCOPUS:85133777550

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

Research Groups and Themes

Keywords

UN SDGs

Access to Document

Handle.net

Fingerprint

Cite this