key: cord-1023634-8z7wo9kz
authors: Chatterjee, Debashree; Tauzin, Alexandra; Marchitto, Lorie; Yu Gong, Shang; Boutin, Marianne; Bourassa, Catherine; Beaudoin-Bussières, Guillaume; Bo, Yuxia; Ding, Shilei; Laumaea, Annemarie; Vézina, Dani; Perreault, Josée; Gokool, Laurie; Morrisseau, Chantal; Arlotto, Pascale; Fournier, Éric; Guilbault, Aurélie; Delisle, Benjamin; Levade, Inès; Goyette, Guillaume; Gendron-Lepage, Gabrielle; Medjahed, Halima; De Serres, Gaston; Tremblay, Cécile; Martel-Laferrière, Valérie; Kaufmann, Daniel E.; Bazin, Renée; Prévost, Jérémie; Moreira, Sandrine; Richard, Jonathan; Côté, Marceline; Finzi, Andrés
title: SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses
date: 2022-01-25
journal: bioRxiv
DOI: 10.1101/2021.12.21.473679
sha: 551989855a1e886437475ce1f7679ff9d7f46adc
doc_id: 1023634
cord_uid: 8z7wo9kz

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naïve and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort recognized and neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

plasmids coding for full-length Spike variants. Two days post-transfection, cells were 102 incubated with the indicated plasmas followed by flow cytometry analysis, as described 103 (Anand et al., 2021; Beaudoin-Bussieres et al., 2020; Gasser et al., 2021; Prevost et al., 104 2020; Tauzin et al., 2021a; Tauzin et al., 2021b) . VOCs Spike expression levels were 105 normalized to the signal obtained with the conformationally independent anti-S2 106 neutralizing CV3-25 antibody (Li et al., 2021; Prevost et al., 2021; Ullah et al., 2021) that 107 efficiently recognized and neutralized all VOCs Spike, including Omicron (Supplemental 108 of some of these mutations with increased infectivity, ACE2 interaction (N501Y, P681H) 151 (Gong et al., 2021; Saito et al., 2021) or immune evasion (K417N, N440K, G446S, S477N, 152 E484A/K, Q493R) (Baum et al., 2020; Clark et al., 2021; Greaney et al., 2021a; Greaney 153 et al., 2021b; Greaney et al., 2021c; Liu et al., 2020; Rappazzo et al., 2021; Starr et al., 154 2021; Weisblum et al., 2020) . This unprecedented accumulation of Spike mutations 155 raised concern about a major antigenic drift that could significantly decrease the efficacy 156 of current vaccines (Andrews et al., 2021; Khoury et al., 2021; Schmidt et al., 2021b) . 157

To get a better understanding of the antigenic profile, we compared the antigenicity of the 159 Omicron Spike to those from D614G, Alpha, Beta, Gamma and Delta VOCs. We used 160 plasma from naïve and previously-infected individuals who received their two doses of 161 the BNT162b2 mRNA vaccine 16 weeks apart. In agreement with previous observations, 162

we found that previously-infected vaccinated individuals recognized more efficiently all second dose) (Stamatatos et al., 2021; Tauzin et al., 2021a; Tauzin et al., 2021b) . 165

Interestingly, we observed that recognition of all Spikes, including Omicron, decreased 166 more rapidly in naïve than previously-infected individuals, as reported (Tauzin et al., 167 2021a) . The three antigenic exposures (infection + 2 doses) of previously-infected against Omicron could also be affected. Of note, low Spike recognition translated into 182 increased Omicron neutralization resistance ( Figure 2C ). In agreement with previous 183 observations ( Stamatatos et al., 2021; Tauzin et al., 2021a; Tauzin et al., 2021b) , plasma 184 from vaccinated previously-infected individuals recognized more efficiently Omicron and 185 all other VOCs than vaccinated naïve individuals ( Figure 1 ). As naïve double-vaccinated 186 levels of plasma binding against Delta Spike in naïve individuals and those against 188

Omicron Spike in previously-infected individuals may be important. This suggests that the 189 benefits of hybrid immunity also apply to Omicron but this hypothesis will need 190 confirmation through vaccine effectiveness studies. with the long interval, n=25 Statistical significance was tested using a Mann-Whitney test 284 (* P < 0.05; ** P < 0.01; *** P < 0.001;**** P < 0.0001). 

Further information and requests for resources and reagents should be directed to and 301 will be fulfilled by the lead contact, Andrés Finzi (andres.finzi@umontreal.ca). 302 303

All unique reagents generated during this study are available from the Lead contact 305 without restriction. 306 307 Data and code availability 308  All data reported in this paper will be shared by the lead contact 309 (andres.finzi@umontreal.ca) upon request. 310  This paper does not report original code. 311  Any additional information required to reanalyze the data reported in this paper is 312 available from the lead contact (andres.finzi@umontreal.ca) upon request. (A) 293T cells were transfected with the full-length Spikes of Omicron possessing either Q493K or Q493R mutation, stained with the CV3-25 Ab or with plasma collected 3 weeks (V3) after the second dose with a 16-week interval from naïve or previouslyinfected donors, represented by red and black points respectively and analyzed by flow cytometry. (B) Neutralizing activity was measured by incubating pseudoviruses bearing SARS-CoV-2 Spikes of the two different Omicron mutants as mentioned above, with serial dilutions of plasma collected 3 weeks (V3) after the second dose with a 16-week interval from naïve donors for 1 h at 37°C before infecting 293T-ACE2 cells. Neutralization half maximal inhibitory serum dilution (ID 50 ) values were determined using a normalized non-linear regression using GraphPad Prism software. Error bars indicate means ± SEM. Statistical significance was tested using a Wilcoxon test (ns, non-significant).

Major role of IgM in the neutralizing activity of 464 convalescent plasma against SARS-CoV-2

Contribution of single mutations to selected 467 SARS-CoV-2 emerging variants Spike antigenicity

Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain 470 that affect recognition by polyclonal human plasma antibodies

Mapping mutations to the SARS-CoV-2 RBD that 474 escape binding by different classes of antibodies

Complete Mapping of Mutations to the 477

SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition

Immunogenicity of Extended mRNA SARS-CoV-2 Vaccine Dosing 481 Intervals

Isolation and characterization of cross-484 neutralizing coronavirus antibodies from COVID-19+ subjects

A meta-486 analysis of Early Results to predict Vaccine efficacy against Omicron

Reduced sensitivity of SARS-CoV-2 variant 499 Delta to antibody neutralization

Cross-Sectional Evaluation of Humoral 502 Responses against SARS-CoV-2 Spike

Spike glycoprotein for host ACE2

A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist 508 genomic epidemiology

SARS-like viruses by an engineered human monoclonal antibody

SARS-CoV-2 spike P681R mutation

Delta variant, enhances viral fusogenicity and pathogenicity

CoV-2 Omicron variant

High genetic barrier to SARS-CoV-2 520 polyclonal neutralizing antibody escape

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