Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

Sokal, Aurélien; Broketa, Matteo; Barba-Spaeth, Giovanna; Meola, Annalisa; 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:10.1016/j.immuni.2022.04.002

Cited by 43 publications

(43 citation statements)

References 48 publications

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“…4B and fig. S8C) ( 11 , 19 ). This difference in antibody binding cross-reactivity is likely due to the presence of shared mutations within the Beta and BA.1 RBDs (E484K/A, K417N, and N501Y) ( 18 ).…”

Section: Resultsmentioning

confidence: 99%

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

et al. 2022

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Understanding immune responses following severe acute respiratory syndrome coronavirus 2 (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, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable 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 VOCs. Together, these findings provide 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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Section: Resultsmentioning

confidence: 99%

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

et al. 2022

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“…Convalescent and BTI sera which neutralized B.1 generally retained good neutralizing ability against Gamma and Delta, while they displayed a substantial decrease in neutralizing ability against Omicron BA.1 ( Figure 1 A–D and Figure 3 A–D) in agreement with previous studies [ 24 , 25 , 26 , 27 , 28 , 45 , 46 , 47 , 48 , 56 , 57 , 68 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 81 , 95 , 99 , 103 , 104 , 105 , 106 ]. It is thought that the ability of Omicron BA.1 to elude NAbs reflects a combination of a higher affinity of the Spike protein for ACE2 [ 20 , 21 , 22 ], together with a TMPRSS-2-independent, endocytosis-mediated entry [ 20 , 107 , 108 ]. Furthermore, the Omicron lineage is phylogenetically and serologically distinct from the previous SARS-CoV-2 lineages.…”

Section: Discussionmentioning

confidence: 99%

“…The Omicron Spike protein also adopts a distinct, more compact conformation and glycosylation patterns that shield it from NAbs [ 23 ]. The fact that prior infection and vaccination do not fully protect against infection with Omicron or symptomatic disease but do partly protect against severe disease [ 109 ] suggests that T-cells and memory B-cells [ 27 , 85 , 107 ], as well as other innate immune signatures [ 110 ] are involved.…”

Section: Discussionmentioning

confidence: 99%

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

Silva

Kohnen

Gilson

et al. 2022

IJMS

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SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.

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“…SARS-CoV-2 variants may have substantial immune evasiveness that weakens vaccine protection due to spike protein mutations (57)(58)(59)(60). Small molecular antivirals have reduced hospitalization rate and mortality in patients with promising safety (181,182), among which Paxlovid stands out by reducing the risk of COVID-19-related hospital admission or death by 89% (183,184).…”

Section: Statins and Covid-19 Antiviralsmentioning

confidence: 99%

“…Different SARS-CoV-2 variants cause resurges of infections (57)(58)(59)(60). Vaccines and antiviral therapies are powerful tools against COVID- 19 (61, 62), yet data regarding the responses of obese individuals or statin users to these agents remain limited.…”

Section: Introductionmentioning

confidence: 99%

Biological Actions, Implications, and Cautions of Statins Therapy in COVID-19

et al. 2022

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The Coronavirus Disease 2019 (COVID-19) showed worse prognosis and higher mortality in individuals with obesity. Dyslipidemia is a major link between obesity and COVID-19 severity. Statins as the most common lipid regulating drugs have shown favorable effects in various pathophysiological states. Importantly, accumulating observational studies have suggested that statin use is associated with reduced risk of progressing to severe illness and in-hospital death in COVID-19 patients. Possible explanations underlie these protective impacts include their abilities of reducing cholesterol, suppressing viral entry and replication, anti-inflammation and immunomodulatory effects, as well as anti-thrombosis and anti-oxidative properties. Despite these benefits, statin therapies have side effects that should be considered, such as elevated creatinine kinase, liver enzyme and serum glucose levels, which are already elevated in severe COVID-19. Concerns are also raised whether statins interfere with the efficacy of COVID-19 vaccines. Randomized controlled trials are being conducted worldwide to confirm the values of statin use for COVID-19 treatment. Generally, the results suggest no necessity to discontinue statin use, and no evidence suggesting interference between statins and COVID-19 vaccines. However, concomitant administration of statins and COVID-19 antiviral drug Paxlovid may increase statin exposure and the risk of adverse effects, because most statins are metabolized mainly through CYP3A4 which is potently inhibited by ritonavir, a major component of Paxlovid. Therefore, more clinical/preclinical studies are still warranted to understand the benefits, harms and mechanisms of statin use in the context of COVID-19.

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Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

Cited by 43 publications

References 48 publications

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

Biological Actions, Implications, and Cautions of Statins Therapy in COVID-19

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