Virus neutralizing antibodies in pseudovirus particle neutralization reaction as a bioanalytical part of a Salnavac® vaccine clinical trial

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Introduction. The SARS-CoV-2 coronavirus pandemic has been a major challenge for all areas of medical science, causing a surge of new developments in various fields ranging from diagnostic techniques to therapeutic and preventive approaches. Intranasal vaccination is an innovative approach to immunization against SARS-CoV-2, which has attracted the attention of many drug developers. Dynamics of blood virus-neutralizing antibodies (VNAs) in recovered COVID-19 patients or vaccinated healthy volunteers is one of the objective parameters for assessing vaccine immunological efficacy, which requires high standards of bioanalytical techniques within the framework of clinical trials. Immunogenicity data on the two-component Salnavak® (intranasal) and Gam-COVID-Vac® (intramuscular) vaccination obtained in randomized double-blind multicenter phase 3 clinical trial interim analysis are presented. The objective of the study was to assess immunogenicity of intranasal and intramuscular vaccination against COVID-19 using a neutralization reaction with pseudoviral particles and HEK293T-hACE2 cell culture. Materials and methods. A total of 137 healthy volunteers with a baseline anti-RBD IgG level not exceeding 100 BAU/ml received immunization by a two-component (Ad26 and Ad5 based) intranasal or intramuscular vaccine administered on day 1 and day 21. Immunogenicity level based on VNA quantitative analysis using a neutralization reaction with pseudoviral particles and a HEK293T-hACE2 cell culture as well as to SARS-CoV-2 S-protein receptor-binding domain (anti-RBD) IgG antibodies on days 21 and 42 after administration of component I was assessed. Results. The geometric mean VNA titer against SARS-CoV-2 on day 42 was 238.34±3.93 and 616.94±3.73 in the Salnavac® and Gam-COVID-Vac® groups, respectively. Trial data shows sufficient immunological efficacy of both intramuscular and intranasal vaccines based on a high protection level at VNA titer of more than 100 while using the pseudoviral neutralization method. The geometric mean of the anti-RBD IgG level by day 42 was 131.22±3.91 and 782.03±3.04 in the Salnavac® and Gam-COVID-Vak® groups, respectively. A direct moderate correlation was shown between VHA and anti-RBD IgG. Conclusion. Neutralization reaction using pseudoviral particles was successfully validated and used to determine the VNA titer during clinical trial. Trial interim data revealed that intranasal vaccine Salnavac® vs intramuscular vaccine Gam-COVID-Vak® resulted in lower but sufficient stringency of humoral immunity.

作者简介

Evgeniy Zuev

JSC “GENERIUM”

Email: evzuev@generium.ru
ORCID iD: 0000-0001-5519-8358
SPIN 代码: 8769-9506

Lead Expert of the Group of Scientific and Medical Expertise and Clinical Development, Department of Scientific Expertise and Pharmacovigilance, Directorate for Clinical Trials and Pharmacovigilance

俄罗斯联邦, Volginsky

Oksana Markova

JSC “GENERIUM”

Email: oamarkova@generium.ru
ORCID iD: 0000-0002-1179-3881

Head of the Department of Scientific Expertise and Pharmacovigilance, Directorate for Clinical Trials and Pharmacovigilance

俄罗斯联邦, Volginsky

Sergey Kulemzin

LLC “IMGEN+”

Email: s.kulemzin@gmail.com
ORCID iD: 0000-0002-4706-623X

PhD (Biology), Researcher

俄罗斯联邦, Novosibirsk

Dmitry Poteryaev

JSC “GENERIUM”

Email: poteryaev@ibcgenerium.ru
ORCID iD: 0000-0003-2695-8869

PhD (Biology), Science Adviser

俄罗斯联邦, Volginsky

Natalya Litvinova

JSC “GENERIUM”

Email: litvinova@ibcgenerium.ru
ORCID iD: 0000-0003-1430-8105

PhD (Biology), Head of Department of Molecular Diagnostics, Department of Pharmaceutical Analysis

俄罗斯联邦, Volginsky

Ilya Korotkevich

JSC “GENERIUM”

Email: iakorotkevich@generium.ru
ORCID iD: 0000-0003-1872-419X

Biostatistician, Group of Biostatistics and Data Management, Department of Scientific Expertise and Pharmacovigilance, Directorate for Clinical Trials and Pharmacovigilance

俄罗斯联邦, Volginsky

Taisiya Grigiryeva

JSC “GENERIUM”

Email: tvgrigorieva@generium.ru
ORCID iD: 0000-0002-8658-7142

Junior Clinical Research Project Manager, Medical Operations Department, Directorate for Clinical Trials and Pharmacovigilance
俄罗斯联邦, Volginsky

Ravil Khamitov

JSC “GENERIUM”

编辑信件的主要联系方式.
Email: khamitov@ibcgenerium.ru
ORCID iD: 0000-0002-1314-894X

 DSc (Medicine), Professor, Vice President of Research and Development

俄罗斯联邦, Volginsky

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2. Figure 1. Distribution of volunteers in the trial

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3. Figure 2. Geometric mean VNA titers and standard deviation in groups of volunteers treated with Salnavac® and Gam-COVID-Vac® Note. VNA — virus-neutralizing antibodies; Y-axis: geometric mean and standard deviation; *the data according published for mRNA-1273 vaccine study (Moderna) [14].

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4. Figure 3. Anti-RBD-IgG concentrations and standard deviation in groups of volunteers treated with Salnavac® and Gam-COVID-Vac®

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版权所有 © Zuev E.V., Kulemzin S.V., Poteryaev D.A., Litvinova N.A., Markova O.A., Korotkevich I.A., Grigiryeva T.V., Kchamitov R.A., 2023

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