Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells

Sokal, Aurélien; Broketa, Matteo; Meola, Annalisa; Barba-Spaeth, Giovanna; Fernández, Ignacio; Fourati, Slim; Azzaoui, Imane; Selle, A.; Vandenberghe, Alexis; Roeser, Anaïs; Bouvier‐Alias, Magali; Crickx, Étienne; Languille, Laetitia; Michel, Marc; Godeau, Bertrand; Gallien, Sébastien; Melica, Giovanna; Nguyen, Yann; Zarrouk, Virginie; Canouï‐Poitrine, Florence; Noizat‐Pirenne, F.; Mégret, Jérôme; Pawlotsky, Jean‐Michel; Fillatreau, Simon; Simon‐Lorière, Etienne; Weill, Jean‐Claude; Reynaud, Claude‐Agnès; Rey, F.A.; Bruhns, Pierre; Chappert, Pascal; Mahévas, Matthieu

doi:10.1101/2021.12.21.473528

Cited by 8 publications

(8 citation statements)

References 22 publications

(13 reference statements)

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“…This is consistent with the observations that neutralizing antibody titers against Omicron are generally low in individuals after two doses of mRNA-1273 or BNT162b2. Nevertheless, Omicron neutralizing antibody titers rapidly increase after a third immunization (Liu et al, 2021;Planas et al, 2021;Schmidt et al, 2021;Sokal et al, 2021b), most likely due to the presence of memory B cells that recognized Omicron RBD, as observed here. Memory B cells may have important contributions in protective immunity by making anamnestic neutralizing antibody responses after infection (Cameroni et al, 2021;Carren ˜o et al, 2021;Cele et al, 2021;Doria-Rose et al, 2021;Gagne et al, 2021;Garcia-Beltran et al, 2021;Zou et al, 2021).…”

Section: Discussionsupporting

confidence: 64%

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

Tarke

Coelho

Zhang

et al. 2022

Cell

643

707

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We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. In subjects ∼6 months post-vaccination, 90% (CD4 + ) and 87% (CD8 + ) of memory T cell responses were preserved against variants on average by AIM assay, and 84% (CD4 + ) and 85% (CD8 + ) preserved against Omicron. Omicron RBD memory B cell recognition was substantially reduced to 42% compared to other variants. T cell epitope repertoire analysis revealed a median of 11 and 10 spike epitopes recognized by CD4 + and CD8 + T cells, with average preservation > 80% for Omicron. Functional preservation of the majority of T cell responses may play an important role as second-level defenses against diverse variants.

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Section: Discussionsupporting

confidence: 64%

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

Tarke

Coelho

Zhang

et al. 2022

Cell

643

707

View full text Add to dashboard Cite

show abstract

“…Earlier studies have shown that neutralizing activity against the Omicron variant is almost exclusive to sera from individuals who have received a booster dose of COVID-19 vaccination virus 19,[34][35][36][37] . However, it has not been clear if the effect of a third vaccine dose on crossprotection is primarily qualitative or quantitative.…”

Section: Discussionmentioning

confidence: 99%

Titers of antibodies the receptor-binding domain (RBD) of ancestral SARS-CoV-2 are predictive for levels of neutralizing antibodies to multiple variants

Tran

Vaage

Mehta

et al. 2022

Preprint

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Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

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“…4A). In contrast to vaccine-induced anti-RBD antibodies, which often show reduced activity against the Beta VOC, only a minority (<5%) of antibodies derived from BA.1 breakthrough donors displayed loss of binding to Beta relative to WT ( 10, 16 ) (Fig. 4B).…”

Section: Main Textmentioning

confidence: 99%

Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

Kaku

Bergeron

Ahlm

et al. 2022

Preprint

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Understanding immune responses following SARS-CoV-2 breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells (MBCs). BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit toward the receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 variants of concern (VOCs). Together, these findings provide fundamental insights into the role of pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.

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Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells

Cited by 8 publications

References 22 publications

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

Titers of antibodies the receptor-binding domain (RBD) of ancestral SARS-CoV-2 are predictive for levels of neutralizing antibodies to multiple variants

Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

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