Rationally designed immunogens enable immune focusing to the SARS-CoV-2 receptor binding motif
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
Eliciting antibodies to surface-exposed viral glycoproteins can lead to protective responses that ultimately control and prevent future infections. Targeting functionally conserved epitopes may help reduce the likelihood of viral escape and aid in preventing the spread of related viruses with pandemic potential. One such functionally conserved viral epitope is the site to which a receptor must bind to facilitate viral entry. Here, we leveraged rational immunogen design strategies to focus humoral responses to the receptor binding motif (RBM) on the SARS-CoV-2 spike. Using glycan engineering and epitope scaffolding, we find an improved targeting of the serum response to the RBM in context of SARS-CoV-2 spike imprinting. Furthermore, we observed a robust SARS-CoV-2-neutralizing serum response with increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses and represents an adaptable design approach for targeting conserved epitopes on other viral glycoproteins.
One Sentence Summary
SARS-CoV-2 immune focusing with engineered immunogens
Article activity feed
-
SciScore for 10.1101/2021.03.15.435440: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experiments were conducted with institutional IACUC approval (MGH protocol 2014N000252). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Immunizations: All immunizations were performed using female C57BL/6 mice (Jackson Laboratory) aged 6-10 weeks. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 150 μL of HRP-conjugated rabbit anti-mouse IgG antibody, sourced commercially from Abcam (at a 1:20,000 dilution in PBS), was used for the secondary incubation. anti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Expi 293F cells (ThermoFisher) were … SciScore for 10.1101/2021.03.15.435440: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experiments were conducted with institutional IACUC approval (MGH protocol 2014N000252). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Immunizations: All immunizations were performed using female C57BL/6 mice (Jackson Laboratory) aged 6-10 weeks. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 150 μL of HRP-conjugated rabbit anti-mouse IgG antibody, sourced commercially from Abcam (at a 1:20,000 dilution in PBS), was used for the secondary incubation. anti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Expi 293F cells (ThermoFisher) were used to express proteins. 293Fsuggested: RRID:CVCL_D615)Transient transfection of 293T cells was used to generate lentiviral particles. 293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)Following incubation, 10,000 293T-ACE2 cells (37) in 20 μL of media containing 15 μg/mL polybrene was introduced to each well. 293T-ACE2suggested: RRID:CVCL_YZ65)Experimental Models: Organisms/Strains Sentences Resources Immunizations: All immunizations were performed using female C57BL/6 mice (Jackson Laboratory) aged 6-10 weeks. C57BL/6suggested: NoneSoftware and Algorithms Sentences Resources Gblocks were then cloned into pVRC and sequence confirmed via Genewiz. Genewizsuggested: (GENEWIZ, RRID:SCR_003177)FlowJo (version 10) was used to analyze FCS files. FlowJosuggested: (FlowJo, RRID:SCR_008520)Nonlinear regressions were fitted to the data using GraphPad Prism (version 9), allowing IC50 values to be calculated via the interpolated 50% inhibitory concentration. 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.
-
