Cross-reactive antibodies after SARS-CoV-2 infection and vaccination
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Curated by eLife
Evaluation Summary:
This study examines whether binding antibodies that cross-react with the spikes of diverse coronaviruses are elicited by SARS-CoV-2 infection. The manuscript is well written, and the figures are laid out in an easy to interpret manner. This study will be of interest to those who are interested in developing pan coronavirus vaccines.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)
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Abstract
Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.
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Evaluation Summary:
This study examines whether binding antibodies that cross-react with the spikes of diverse coronaviruses are elicited by SARS-CoV-2 infection. The manuscript is well written, and the figures are laid out in an easy to interpret manner. This study will be of interest to those who are interested in developing pan coronavirus vaccines.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)
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Reviewer #1 (Public Review):
The results shown by Grobben et al. are basically important and should be published for the post-vaccination era. However, the cross-reactivity is mostly evaluated by only the binding affinity to the S proteins. The authors should evaluate the neutralizing activity of these antibodies using live viruses and/or pseudoviruses. Using all coronaviruses might be difficult, but some (e.g., seasonal coronaviruses such as 229E and NL63) should be used.
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Reviewer #2 (Public Review):
Here the authors were seeking to assess whether SARS-CoV-2 infection elicited antibodies that cross react with diverse human CoVs using a Luminex platform. The major conclusions are that cross-binding antibodies are elicited by SARS-CoV-2 infection, and that there is a positive association between the magnitude of the response and the sequence similarity to SARS-CoV-2. As a result, most cross-reactive antibodies target the S2 region which is the most conserved among diverse CoVs. The study also shows that immunization with a SARS-CoV-2 spike derived nanoparticle vaccine similarly elicits cross reactive CoV antibodies in non-human primates. Overall, the data suggests that the S2 domain might be important for the development of pan CoV vaccines.
The study is largely observational, and conclusions are supported …
Reviewer #2 (Public Review):
Here the authors were seeking to assess whether SARS-CoV-2 infection elicited antibodies that cross react with diverse human CoVs using a Luminex platform. The major conclusions are that cross-binding antibodies are elicited by SARS-CoV-2 infection, and that there is a positive association between the magnitude of the response and the sequence similarity to SARS-CoV-2. As a result, most cross-reactive antibodies target the S2 region which is the most conserved among diverse CoVs. The study also shows that immunization with a SARS-CoV-2 spike derived nanoparticle vaccine similarly elicits cross reactive CoV antibodies in non-human primates. Overall, the data suggests that the S2 domain might be important for the development of pan CoV vaccines.
The study is largely observational, and conclusions are supported by the data. The major limitation is that it is not clear what role the measured cross-reactive antibodies might play in protective immunity. If a function could be assigned to the cross-reactive antibodies ie neutralization or ADCC, then these findings might be more impactful for guiding the design of pan CoV vaccines.
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SciScore for 10.1101/2021.05.26.21256092: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Centre, location AMC, the Netherlands and approved by the local ethical committee (NL 73281.018.20).
Consent: All individuals provided written informed consent before participating.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
Experimental Models: Cell Lines Sentences Resources All other proteins were produced in HEK293F cells (Invitrogen) maintained in Freestyle medium (Life Technologies). HEK293Fsuggested: RRID:CVCL_6642)Briefly, HEK293T cells expressing the SARS-CoV-2 receptor ACE2 were seeded in poly-L-lysine coated 96-wells plates and the next day triplicate … SciScore for 10.1101/2021.05.26.21256092: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Centre, location AMC, the Netherlands and approved by the local ethical committee (NL 73281.018.20).
Consent: All individuals provided written informed consent before participating.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
Experimental Models: Cell Lines Sentences Resources All other proteins were produced in HEK293F cells (Invitrogen) maintained in Freestyle medium (Life Technologies). HEK293Fsuggested: RRID:CVCL_6642)Briefly, HEK293T cells expressing the SARS-CoV-2 receptor ACE2 were seeded in poly-L-lysine coated 96-wells plates and the next day triplicate serial dilutions of heat-inactivated serum samples were prepared, mixed 1:1 with SARS-CoV-2 pseudovirus, incubated for 1 h at 37°C and then added in a 1:1 ratio to the cells. HEK293Tsuggested: NoneRecombinant DNA Sentences Resources Specifically, a gene encoding amino acids 1-1276, in which the furin cleavage site (amino acids 752-756) was replaced with a GGSGS sequence and amino acids at position 1067 and 1068 were mutated to prolines, was ordered and cloned into a pPPI4 plasmid containing a T4 trimerization domain followed by a hexahistidine tag. pPPI4suggested: NoneSoftware and Algorithms Sentences Resources Mann-Whitney U-tests for unpaired comparisons, Wilcoxon matched-pairs signed rank test for paired comparisons and Spearman correlations were performed in GraphPad Prism 8.3.0. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Principal component analysis was performed in Matlab 9.6 (R2019a). Matlabsuggested: (MATLAB, RRID:SCR_001622)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.
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