Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

Tong, Pei; Gautam, Avneesh; Windsor, Ian W.; Travers, Meghan; Chen, Yuezhou; Garcia, Nicholas; Whiteman, Noah B.; McKay, Lindsay; Storm, Nadia; Malsick, Lauren; Honko, Anna N.; Lelis, Felipe J.N.; Habibi, Shaghayegh; Jenni, Simon; Cai, Yongfei; Rennick, Linda J.; Duprex, W. Paul; McCarthy, K.; Lavine, Christy L.; Zuo, Teng; Lin, Junrui; Zuiani, Adam; Feldman, Jared; MacDonald, Elizabeth A.; Hauser, Blake M.; Griffiths, Anthony; Seaman, Michael S.; Schmidt, Aaron; Chen, Bing; Neuberg, Donna; Bajic, Goran; Harrison, Stephen C.; Wesemann, Duane R.

doi:10.1016/j.cell.2021.07.025

Cited by 99 publications

(114 citation statements)

References 60 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…Several studies reported on the humoral response following the BNT162b2 mRNA COVID-19 vaccination and found that SARS-CoV-2 antibody titers 4 to 6 months after infection decline more slowly than in the initial months after the infection (Ebinger et al, 2021; Padoan et al, 2021; Tré-Hardy et al, 2021). At least two recent studies reported that antibodies could be detected up to 11 months after infection and provided evidence that that these antibodies originated in memory B cells, not plasmablasts(Tong et al, 2021; Turner et al, 2021a). Generation of SARS-CoV-2 memory B cells(De Gasparo et al, 2021; Schoof et al, 2020; Xu et al, 2021) is likely necessary for long-term protection since that is the mechanism by which most anti-viral vaccines work(Iwasaki, 2016).…”

Section: Discussionmentioning

confidence: 99%

Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Israel

Shenhar

Green

et al. 2021

Preprint

110

View full text Add to dashboard Cite

BackgroundImmune protection following either vaccination or infection with SARS-CoV-2 decreases over time.ObjectiveTo determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals.MethodsAntibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine.ResultsA total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection.ConclusionsThis study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.FundingThis research was internally funded by Leumit Health Services (LHS) and was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research.The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Impact statementLarge scale study display the kinetics of SARS-CoV-2 IgG antibodies present in individuals vaccinated with two doses of mRNA vaccine vs. unvaccinated patients who had recovered from the disease: initial levels of antibody are much higher in vaccinated patients, but decrease faster.

show abstract

Section: Discussionmentioning

confidence: 99%

Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Israel

Shenhar

Green

et al. 2021

Preprint

110

View full text Add to dashboard Cite

show abstract

“…Importantly, the RBD is also the primary target of the neutralizing antibodies elicited by natural infection or vaccination (Box 1 ). There are three major non-overlapping antigenic sites on the RBD 52 (Fig. 2a ).…”

Section: Coronavirus S Proteinmentioning

confidence: 99%

Mechanisms of SARS-CoV-2 entry into cells

Jackson

Farzan

Chen

et al. 2021

Nat Rev Mol Cell Biol

Self Cite

2,028

1,841

View full text Add to dashboard Cite

The unprecedented public health and economic impact of the COVID-19 pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been met with an equally unprecedented scientific response. Much of this response has focused, appropriately, on the mechanisms of SARS-CoV-2 entry into host cells, and in particular the binding of the spike (S) protein to its receptor, angiotensin-converting enzyme 2 (ACE2), and subsequent membrane fusion. This Review provides the structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the S protein with ACE2, engagement of the receptor-binding domain of the S protein with ACE2, proteolytic activation of the S protein, endocytosis and membrane fusion. We define the roles of furin-like proteases, transmembrane protease, serine 2 (TMPRSS2) and cathepsin L in these processes, and delineate the features of ACE2 orthologues in reservoir animal species and S protein adaptations that facilitate efficient human transmission. We also examine the utility of vaccines, antibodies and other potential therapeutics targeting SARS-CoV-2 entry mechanisms. Finally, we present key outstanding questions associated with this critical process.

show abstract

“…However, the widespread emergence of viral variants that evade neutralization by preformed antibodies present in convalescent serum will likely significantly decrease the duration of antibody-mediated immunity elicited by SARS-CoV-2 infection 74 , 75 . In these cases, protection against severe disease will be reliant on the reactivation of somatically mutated memory B cells that recognize antigenically distinct viral variants, which is discussed further in the next section 40 , 76 , 77 .…”

Section: B Cell Response To Sars-cov-2 Infectionmentioning

confidence: 99%

The germinal centre B cell response to SARS-CoV-2

2021

View full text Add to dashboard Cite

The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC response has profound implications for the capacity of responding B cells to contribute to protection against infection. However, direct assessment of the GC response in humans remains a major challenge. Here we summarize emerging evidence for the importance of the GC response in the establishment of durable and broad immunity against SARS-CoV-2 and discuss new approaches to modulate the GC response to better protect against newly emerging SARS-CoV-2 variants. We also discuss new findings showing that the GC B cell response persists in the draining lymph nodes for at least 6 months in some individuals following vaccination with SARS-CoV-2 mRNA-based vaccines.

show abstract

Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

Cited by 99 publications

References 60 publications

Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Mechanisms of SARS-CoV-2 entry into cells

The germinal centre B cell response to SARS-CoV-2

Contact Info

Product

Resources

About