Immune recall improves antibody durability and breadth to SARS-CoV-2 variants
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
Key features of immune memory are greater and faster antigen-specific antibody responses to repeat infection. In the setting of immune-evading viral evolution, it is important to understand how far antibody memory recognition stretches across viral variants when memory cells are recalled to action by repeat invasions. It is also important to understand how immune recall influences longevity of secreted antibody responses. We analyzed SARS-CoV-2 variant recognition; dynamics of memory B cells; and secreted antibody over time after infection, vaccination, and boosting. We find that a two-dose SARS-CoV-2 vaccination regimen given after natural infection generated greater longitudinal antibody stability and induced maximal antibody magnitudes with enhanced breadth across Beta, Gamma, Delta and Omicron variants. A homologous third messenger RNA vaccine dose in COVID-naïve individuals conferred greater cross-variant evenness of neutralization potency with stability that was equal to the hybrid immunity conferred by infection plus vaccination. Within unvaccinated individuals who recovered from COVID, enhanced antibody stability over time was observed within a subgroup of individuals who recovered more quickly from COVID and harbored significantly more memory B cells cross-reactive to endemic coronaviruses early after infection. These cross-reactive clones map to the conserved S2 region of SARS-CoV-2 spike with higher somatic hypermutation levels and greater target affinity. We conclude that SARS-CoV-2 antigen challenge histories in humans influence not only the speed and magnitude of antibody responses but also functional cross-variant antibody repertoire composition and longevity.
Article activity feed
-
-
SciScore for 10.1101/2021.09.09.459504: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Human subjects: Mass General Brigham Institutional Review Board approved this study and protocol. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources For the anti-S and anti-RBD antibody standard, the monoclonal antibody CR3022 was serially diluted 2 times from 0.5 μg/mL. anti-Ssuggested: Noneanti-RBDsuggested: NoneCells were stained with Biolegend antibodies FITC anti-CD27 (356404), PE anti-CCR7 (353204), Percp anti-CD27suggested: (BioLegend Cat# 356404, RRID:AB_2561788)anti-CCR7suggested: NoneExperimental Models: Cell Lines Sentences Resources Cell… SciScore for 10.1101/2021.09.09.459504: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Human subjects: Mass General Brigham Institutional Review Board approved this study and protocol. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources For the anti-S and anti-RBD antibody standard, the monoclonal antibody CR3022 was serially diluted 2 times from 0.5 μg/mL. anti-Ssuggested: Noneanti-RBDsuggested: NoneCells were stained with Biolegend antibodies FITC anti-CD27 (356404), PE anti-CCR7 (353204), Percp anti-CD27suggested: (BioLegend Cat# 356404, RRID:AB_2561788)anti-CCR7suggested: NoneExperimental Models: Cell Lines Sentences Resources Cell lines: HEK293T cell line (ATCC) was maintained in DMEM containing 10% FBS, 100 U/mL penicillin and 100 U/mL streptomycin (Gibco). HEK293Tsuggested: NoneSARS-CoV-2 pseudovirus neutralization assay: 293T cells were co-transfected with pHDM vector expressing SARS-CoV-2 variants, pLenti CMV Puro LUC (w168-1), and psPAX2 (Addgene) with lipofetamine 3000. 293Tsuggested: NoneRecombinant DNA Sentences Resources To be consistent with the pHDM-Wuhan-Hu-1-delta21 and pHDM-D614G-delta21 plasmids obtained from Addgene, the c-terminal 21 amino acid on all the variants were deleted (Crawford et al., 2020). pHDM-Wuhan-Hu-1-delta21suggested: NonepHDM-D614G-delta21suggested: NoneBinding signals were scored positive if OD405 values were above 5x PBS control on the same plate. mAb spike binding EC50 measurement: 293T cells were co-transfected with pHDM-Wuhan-Hu-1 and pMAX-GFP plasmids at a 4:1 ratio by lipofectamine 3000 (Thermo fisher). pHDM-Wuhan-Hu-1suggested: NonepMAX-GFPsuggested: RRID:Addgene_16007)293T cell pool cotransfected with pHEF-VsVg and pMAX-GFP plasmids at a 4:1 ratio was used as a negative control. pHEF-VsVgsuggested: RRID:Addgene_22501)SARS-CoV-2 pseudovirus neutralization assay: 293T cells were co-transfected with pHDM vector expressing SARS-CoV-2 variants, pLenti CMV Puro LUC (w168-1), and psPAX2 (Addgene) with lipofetamine 3000. pHDMsuggested: NonepsPAX2suggested: RRID:Addgene_12260)Software and Algorithms Sentences Resources After enrollment, clinical team identified one subject was not diagnosed by nasopharyngeal swab RT-PCR test, but by Quest Diagnostics antibody test and symptoms consistent with COVID-19 (Chen et al., 2020). Questsuggested: (QUEST, RRID:SCR_005210)Graphpad software generated standard curves for each plate by non-linear regression. Graphpadsuggested: (GraphPad, RRID:SCR_000306)The EC50 for each S-binding mAb was reported as the concentration with 50% of maximal binding determined by non-linear regression using Graphpad Prism. Graphpad Prismsuggested: (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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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.
-
