key: cord-0782721-ldbowfrl
authors: Sanchez-Sendra, B.; Albert, E.; Zulaica, J.; Torres, I.; Gimenez, E.; Botija, P.; Beltran, M. J.; Rodado, C.; Geller, R.; Navarro, D.
title: Neutralizing antibodies against SARS-CoV-2 variants of concern elicited by the Comirnaty COVID-19 vaccine in nursing home residents
date: 2021-10-07
journal: nan
DOI: 10.1101/2021.10.06.21264607
sha: 6281160d55c30c3720b83c1a1bc2309dc7825486
doc_id: 782721
cord_uid: ldbowfrl

Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty COVID-19-vaccinated elderly nursing home residents (n=30) or younger individuals (n=18) and non-vaccinated individuals who recovered from severe COVID-19 (n=19). In all groups, some participants lacked NtAb against one or more VOCs, mainly the Beta variant (15-20%). Serum NtAb titers were lowest against the Beta variant followed by Gamma, Epsilon, and Delta variants. Fold change reduction in NtAb titers relative to the ancestral strain was greatest for the Beta variant (6.7-18.8) followed by Gamma (3.6-6.2), Epsilon (2.9-5.8), and Delta (3.5-4.3) variants, regardless of the study group considered. In summary, older age, frailty, and concurrence of co-morbidities had no impact on the serum NtAb activity profile against SARS-CoV-2 VOCs.

Coronaviruses encode a proof-reading mechanism to minimize sequence variation in the which may pose a threat to pandemic control due to their relative resistance to the SARS-CoV-2 nucleoprotein (N), and 8 had contracted COVID-19 requiring 1 hospitalization prior to receiving the first dose of the Comirnaty® COVID-19 vaccine, 2 as determined by positive RT-PCR results in nasopharyngeal specimens and the 3 detection of SARS-CoV-2 N antibodies. In all cases, the variant Wuhan/D614G was 4 involved, as determined by whole-genome sequencing (not shown). All participants in D614G mutation was introduced by site-directed mutagenesis. Subsequently, additional L452R, D614G), a synthetic fragment encoding mutations S13I, W152C, and L452R 1 6 was cloned. All plasmids were verified by Sanger sequencing.

Virus neutralization assay 1 8 The neutralization capacity of circulating antibodies (NtAb) against the SARS-CoV-2 S was quantified using a live-cell microscope (Incucyte S3, Sartorius). Background

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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Fisher's exact test. Two-sided exact P values were reported. A P value <0.05 was 5 considered statistically significant. The analyses were performed using SPSS version Antibodies targeting the SARS-CoV-2 RBD were detectable in all but one (belonging to 1 1 group 3) out of the 67 participants and in none of the controls. Antibody levels across 1 2 the study groups, shown in Figure 1 , were found to differ significantly, with nursing 1 3 home residents displaying higher levels as compared to that in participants from the 1 4 other two study groups. Similarly, using a pseudotyped vesicular stomatitis virus 1 5 system, NtAb against the ancestral strain were detected in all but one (belonging group 1 6 3) participants and in none of the controls. Measurable NtAb against the different 1 7 SARS-CoV-2 VOCs included in the study were found at variable frequencies depending 1 8 upon the study group and the virus variant considered (Table 1 ). In all groups, some 1 9

participants lacked NtAb against one or more VOCs, most notably the Beta variant (15-2 0 20%). As for vaccinated individuals (groups 1 and 2), no significant differences in the 2 1 detection rate of NtAb for any SARS-CoV-2 VOCs were found (P≥0.5) ( Table 1 ).

Antibody neutralizing titers against SARS-CoV-2 S variants across study groups 2 3 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Overall, all VOCs were neutralized to a lesser extent than the ancestral strain ( Figure 2 ). 1 Specifically, serum NtAb titers were lowest against the Beta variant followed by 2 Gamma, Epsilon, and Delta variants, although wide ranges were observed for all 3 variants. This pattern was shared by all study groups (Figure 3 and Table 2 ). 4 Accordingly, fold change reduction in NtAb titers relative to the ancestral strain was 5 greatest for the Beta variant (6.7-18.8) followed by Gamma (3.6-6.2), Epsilon (2.9-5.8), The degree of correlation between levels of SARS-CoV-2 antibodies neutralizing 1 0 SARS-CoV-2 VOCs and total anti-RBD antibodies across the different population 1 1 groups was examined next. Overall, the correlation between these two parameters was Table 1 ). Reduced neutralization of VOCs as compared to the ancestral Wuhan-Hu-1 strain has 1 7 been observed in sera from individuals that were fully vaccinated against SARS-CoV-2 Here, using S-pseudotyped SARS-CoV-2 variants, we extend this finding to include 2 4 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.06.21264607 doi: medRxiv preprint elderly nursing home residents, both in SARS-CoV-2 naïve participants and those 1 infected by the Wuhan/D614G variant prior to vaccination. In effect, one month after 2 the second vaccine dose, sera from fully vaccinated nursing home residents retained the 3 ability to neutralize VOCs in most cases, but did so to a lesser extent than the ancestral 4 strain, especially in the case of the Beta variant. Importantly, reduction in NtAb activity 5 against VOCs in this population group was not significantly different from that seen in vaccinees, our data strongly support the idea that older age, frailty, and concurrence of 1 1 co-morbidities in fully-vaccinated individuals had no impact on the serum NtAb activity Wuhan-Hu-1 reference strain (fold-change reduction in NtAb activity) was higher for NtAb activity against Beta and Delta variants, respectively, for sera from participants in 1 8 the Comirnaty® COVID-19 vaccine the trial, who were seemingly comparable to our 1 9 healthy vaccinated controls (13.1 and 3.0 fold reduction, respectively). In turn, using The relatively small sample size could be considered a limitation of the current study. Also, a limitation inherent to the use of S-pseudotyped viruses is the inability to assess reduction in NtAb activity in this population group was not different from that seen in 2 3 vaccinated controls and recovered COVID-19 individuals who had not been vaccinated.

Importantly, among VOCs, the Delta variant that is currently predominant worldwide December 10, 2020. SARS-CoV-2 spike protein variants. Elife. 2020;9:e61312.

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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Relative to the NtAb titer against WA1/2020. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.06.21264607 doi: medRxiv preprint

Coronaviruses lacking 4 exoribonuclease activity are susceptible to lethal mutagenesis: evidence for