key: cord-0886853-wt5qxe0j
authors: Dolzhikova, I. V.; Iliukhina, A. A.; Kovyrshina, A. V.; Kuzina, A. V.; Gushchin, V. A.; Siniavin, A. E.; Pochtovyi, A. A.; Shidlovskaya, E. V.; Kuznetsova, N. A.; Megeryan, M. M.; Dzharullaeva, A. S.; Erokhova, A. S.; Izhaeva, F. M.; Grousova, D. M.; Botikov, A. G.; Shcheblyakov, D. V.; Tukhvatulin, A. I.; Zubkova, O. V.; Logunov, D. Y.; Gintsburg, A. L.
title: Sputnik Light booster after Sputnik V vaccination induces robust neutralizing antibody response to B.1.1.529 (Omicron) SARS-CoV-2 variant
date: 2021-12-21
journal: nan
DOI: 10.1101/2021.12.17.21267976
sha: 21205e4a517726cd0c30db980755a26cac1c9bae
doc_id: 886853
cord_uid: wt5qxe0j

COVID-19 vaccination campaign has been launched around the world. More than 8 billion vaccines doses have been administered, according to the WHO. Published studies shows that vaccination reduces the number of COVID-19 cases and dramatically reduces COVID-19-associated hospitalizations and deaths worldwide. In turn, the emergence of SARS-CoV-2 variants of concern (VOC) with mutations in the receptor-binding domain (RBD) of S glycoprotein poses risks of diminishing the effectiveness of the vaccination campaign. In November 2021, the first information appeared about a new variant of the SARS-CoV-2 virus, which was named Omicron. The Omicron variant is of concern because it contains a large number of mutations, especially in the S glycoprotein (16 mutation in RBD), which could be associated with resistance to neutralizing antibodies (NtAB) and significantly reduce the effectiveness of COVID-19 vaccines. Neutralizing antibodies are one of the important parameters characterizing the protective properties of a vaccine. We conducted a study of neutralizing antibodies in the blood serum of people vaccinated with Sputnik V, as well as those revaccinated with Sputnik Light after Sputnik V. Results showed that a decrease in the level of neutralizing antibodies was observed against SARS-CoV-2 Omicron (B.1.1.529) variant in comparison to B.1.1.1 variant. Analysis of the sera of individuals vaccinated with Sputnik V 6-12 months ago showed that there was a decrease in the level of neutralizing antibodies by 11.76 folds. While no direct comparison with other vaccines declines has been done in this study, we note their reported decline in antibody neutralization at a much more significant level of 40-84 times. At the same time, the analysis of sera of individuals who were vaccinated with Sputnik V, and then revaccinated Sputnik Light, showed that 2-3 months after revaccination the decrease in the level of neutralizing antibodies against the Omicron variant was 7.13 folds. Despite the decrease in NtAb, we showed that all revaccinated individuals had NtAb to Omicron variant. Moreover, the NtAb level to Omicron variant in revaccinated sera are slightly higher than NtAb to B.1.1.1 in vaccinated sera.

ChAdOx1 prime/BNT162b2 boost [3] . The neutralization activity against B.1.1.529 was higher in sera from superimmune individuals with hybrid immunity (infected and vaccinated or vaccinated and infected) [3] [4] [5] . In conditions of decreasing virus neutralizing activity of antibodies, T-cell mediated immunity becomes an essential barrier to prevent severe COVID-19 [5] . vaccines that can elicit post-vaccinal T-cell immunity should be studied.

We performed analysis of neutralization antibody in sera samples of individuals vaccinated with recombinant adenoviral-based vaccine Sputnik V (rAd26-S + rAd5-S) and revaccinated with Sputnik Light vaccine (rAd26-S). We isolated the viable SARS-CoV-2 virus Omicron variant (B.1.1.529) from a patient who arrived from South Africa ( Figure 1 ). The virus was genetically characterized (hCoV-19/Russia/MOW-Moscow_PMVL-O16/2021) and used to analyze the virusneutralizing activity of the sera of vaccinated and revaccinated individuals. The study was conducted with sera from people who were vaccinated with Sputnik V 6-12 months ago, as well as sera from people who were revaccinated with Sputnik Light 2-3 months ago (Table S1 ). RBD-specific IgG was detected in all analyzed sera samples ( Figure 2 ). All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 21, 2021. ; perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 21, 2021. ; Figure 3 . Titers of neutralizing antibodies in blood sera samples of individuals vaccinated with Sputnik V and revaccinated with Sputnik Light. The figure shows individual data for the studied sera, geometric mean and 95% confidence interval. The figure shows the p-value (Wilcoxon test), % of individuals with detectable NtAb to the SARS-CoV-2, geometric mean and the level of NtAb reduction. Grey boxlimit of detection. Values below the limit of detection were assigned a value of NtAb 1.25.

Our data show that vaccination with Sputnik V and revaccination with Sputnik Light allows to induce robust neutralizing antibody response. We see that the NtAb decrease against the Omicron variant is the most significant than against the other SARS-CoV-2 variants of concern (VOCs). In perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted December 21, 2021. ; https://doi.org/10.1101/2021.12.17.21267976 doi: medRxiv preprint over time of neutralizing antibodies to the Omicron variant after vaccination and revaccination.

Additional work is currently underway to study the level of neutralizing antibodies in expanded sample sizes, as well as to study the effectiveness of the Sputnik V vaccine against Omicron variant in a lethal model in hACE2-transgenic mice.

Further studies are important to understand the effectiveness of COVID-19 vaccines against the new SARS-CoV-2 Omicron variant. If there will be a critical decrease in effectiveness (lower than recommended by WHO), it is necessary to consider change the antigenic composition of the vaccines. In this case, the efficacy of the new vaccine candidate should be studied against Omicron, as well as Delta, the proportion of which remains prevalent.

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Local Ethics Committee of Gamaleya NRCEM (Protocol No. 17 of December 03, 2021).

Peripheral blood was collected from vaccinated individuals after the Sputnik V vaccination and after the Sputnik Light revaccination (Table S1 ). The blood was centrifuged at 1000g for 10 minutes. The serum was aliquoted and stored at -80°C until use. RBD-specific IgG was determined by ELISA kit «SARS-CoV-2-RBD-ELISA-GAMALEYA» (P3H 2020/10393 2020-05-18).

Before performing the neutralization assay, the serum was thawed and inactivated at +56°C for 30 minutes.

The virus was isolated from a nasopharyngeal swab of a patient who arrived from South Africa. Sample preparation of RNA for sequencing and sequencing were carried out according to the method described earlier [6] .

Vero E6 cells were used for isolation, initial passage, propagation and titration. Vero E6 cells were maintained in complete Dulbecco's modified Eagle's medium (DMEM, HyClone Cytiva, Austria), containing 10% heat-inactivated fetal bovine serum (HI-FBS, Capricorn scientific, Germany), L-glutamine (4 mM, PanEco, Russia), penicillin/streptomycin solution (100

GISAID

SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals, medRxiv

SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection

Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies, medRxiv

Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants

All rights reserved. No reuse allowed without permission. perpetuity

preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted