Hybrid immunity improves B cell frequency, antibody potency and breadth against SARS-CoV-2 and variants of concern
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
To understand the nature of the antibody response to SARS-CoV-2 vaccination, we analyzed at single cell level the B cell responses of five naïve and five convalescent people immunized with the BNT162b2 mRNA vaccine. Convalescents had higher frequency of spike protein specific memory B cells and by cell sorting delivered 3,532 B cells, compared with 2,352 from naïve people. Of these, 944 from naïve and 2,299 from convalescents produced monoclonal antibodies against the spike protein and 411 of them neutralized the original Wuhan SARS-CoV-2 virus. More than 75% of the monoclonal antibodies from naïve people lost their neutralization activity against the B.1.351 (beta) and B.1.1.248 (gamma) variants while this happened only for 61% of those from convalescents. The overall loss of neutralization was lower for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants, however it was always significantly higher in those of naïve people. In part this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in convalescents and generated potent and broadly neutralizing antibodies. Overall, vaccination of seropositive people increases the frequency of B cells encoding antibodies with high potency and that are not susceptible to escape by any of the four variants of concern. Our data suggest that people that are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control SARS-CoV-2 emerging variants.
Article activity feed
-
SciScore for 10.1101/2021.08.12.456077: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Enrollment of COVID-19 vaccinees and human sample collection: This work results from a collaboration with the Azienda Ospedaliera Universitaria Senese, Siena (IT) that provided samples from COVID-19 vaccinated donors, of both sexes, who gave their written consent.
IRB: The study was approved by local ethics committees (Parere 17065 in Siena) and conducted according to good clinical practice in accordance with the declaration of Helsinki (European Council 2001, US Code of Federal Regulations, ICH 1997).Sex as a biological variable Enrollment of COVID-19 vaccinees and human sample collection: This work results from a collaboration with the Azienda Ospedaliera Universitaria Senese, Siena … SciScore for 10.1101/2021.08.12.456077: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Enrollment of COVID-19 vaccinees and human sample collection: This work results from a collaboration with the Azienda Ospedaliera Universitaria Senese, Siena (IT) that provided samples from COVID-19 vaccinated donors, of both sexes, who gave their written consent.
IRB: The study was approved by local ethics committees (Parere 17065 in Siena) and conducted according to good clinical practice in accordance with the declaration of Helsinki (European Council 2001, US Code of Federal Regulations, ICH 1997).Sex as a biological variable Enrollment of COVID-19 vaccinees and human sample collection: This work results from a collaboration with the Azienda Ospedaliera Universitaria Senese, Siena (IT) that provided samples from COVID-19 vaccinated donors, of both sexes, who gave their written consent. Randomization This study was unblinded and not randomized. Blinding not detected. Power Analysis No statistical methods were used to predetermine sample size. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-Human IgG −Peroxidase antibody (Fab specific) produced in goat (Sigma) diluted 1:45000 in sample buffer was then added and samples were incubated for 1 h at 37°C. Anti-Human IgG −Peroxidase antibodysuggested: NoneAnti-Human IgGsuggested: (Abcam Cat# ab45000, RRID:AB_732293)Experimental Models: Cell Lines Sentences Resources The mixture was then added to the wells of a 96-well plate containing a sub-confluent Vero E6 cell monolayer. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Analysis was performed using FlowJo (version 10). FlowJosuggested: (FlowJo, RRID:SCR_008520)Statistical analysis: Statistical analysis was assessed with GraphPad Prism Version 8.0.2 ( GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPad Software, Inc. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:One limitation of our study is that we did not include people that received a third booster dose of vaccine, as at the time that this work was being performed no policies for a third booster dose were implemented. In spite of this limitation, we believe that our conclusions are likely to be extendable to people that are seropositives following primary vaccination. Indeed, the S protein produced following vaccination with mRNA, viral vectors or following infection is produced in all cases by the cell of the host and it is likely to be presented to the immune system in a similar manner and generate a similar antibody response. This is confirmed by the fact that neutralizing antibodies following infection and vaccination derive mostly from the same immunodominant germlines, i.e. IGHV3-53, 3-30 and 3-669,10,16,17. Our analysis suggests that a booster dose of vaccine will increase the frequency of memory B cells producing potent neutralizing antibodies not susceptible to escape variants and allow better control of this pandemic. Our work also shows that more than three quarters of antibodies neutralizing the Wuhan virus do not neutralize at all the beta and gamma variants, while the fraction of antibodies not neutralizing the alpha and delta variants is much smaller and in all cases below 50%. This suggest that the beta and gamma variants were originally selected to escape natural immunity, while the alpha and gamma were selected mostly for their increased infectivity and ability ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-