Nucleocapsid-specific humoral responses improve the control of SARS-CoV-2
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Abstract
The spike protein of SARS-CoV-2 is a critical antigen present in all approved SARS-CoV-2 vaccines. This surface viral protein is also the target for all monoclonal antibody therapies, but it is unclear whether antibodies targeting other viral proteins can also improve protection against COVID-19. Here, we interrogate whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine, and then transferred sera from these mice into naïve mice. On the next day, the recipient mice were challenged intranasally with SARS-CoV-2 to evaluate whether nucleocapsid-specific humoral responses affect viral control. Interestingly, mice that received nucleocapsid-specific sera exhibited enhanced control of a SARS-CoV-2 infection. These findings provide the first demonstration that humoral responses specific to an internal coronavirus protein can help clear infection, warranting the inclusion of other viral antigens in next-generation SARS-CoV-2 vaccines and providing a rationale for the clinical evaluation of nucleocapsid-specific monoclonals to treat COVID-19.
Highlights
A SARS-CoV-2 nucleocapsid vaccine elicits robust nucleocapsid-specific antibody responses.
This nucleocapsid vaccine generates memory B cells (MBC).
Nucleocapsid-specific humoral responses do not prevent SARS-CoV-2 infection.
Nucleocapsid-specific humoral responses help control a SARS-CoV-2 infection.
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SciScore for 10.1101/2022.03.09.483635: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures were performed with the approval of the center for comparative medicine at Northwestern University and the UIC IACUC. Sex as a biological variable Adult mice, approximately half females and half males were used for the immunogenicity experiments included in this study. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Cells were not authenticated as they were purchased from a reputable vendor and certificate of analysis was obtained. Table 2: Resources
Antibodies Sentences Resources Cells were stained with fluorescently-labeled antibodies against CD8α (53-6.7 on PerCP-Cy5.5), CD44 (IM7 on Pacific Blue), and KbN219 … SciScore for 10.1101/2022.03.09.483635: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All procedures were performed with the approval of the center for comparative medicine at Northwestern University and the UIC IACUC. Sex as a biological variable Adult mice, approximately half females and half males were used for the immunogenicity experiments included in this study. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Cells were not authenticated as they were purchased from a reputable vendor and certificate of analysis was obtained. Table 2: Resources
Antibodies Sentences Resources Cells were stained with fluorescently-labeled antibodies against CD8α (53-6.7 on PerCP-Cy5.5), CD44 (IM7 on Pacific Blue), and KbN219 (PE). CD8αsuggested: NoneCD44suggested: NoneSARS-CoV-2 nucleocapsid specific ELISA: Binding antibody titers were quantified using ELISA as described previously (Dangi et al., 2020; Palacio et al., 2020), using nucleocapsid protein as coating antigens. using nucleocapsid protein as coating antigens.suggested: NoneExperimental Models: Cell Lines Sentences Resources Vero E6 cells were used to propagate SARS CoV-2 isolate USA-WA1/2020 (BEI resources, NR-52281). Vero E6suggested: NoneThe Ad5 vector was propagated on trans-complementing HEK293 cells (ATCC), purified by cesium chloride density gradient centrifugation, titrated, and then frozen at −80□°C. HEK293suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)In brief, Vero cells were passaged in DMEM with 10% Verosuggested: NoneViral titers were determined by plaque assay on Vero-E6 cells. Vero-E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources K18-hACE2 mice were anesthetized with isoflurane and challenged with 103 PFU of SARS-CoV-2 intranasally. K18-hACE2suggested: RRID:IMSR_GPT:T037657)Software and Algorithms Sentences Resources Flow cytometry samples were acquired with a Becton Dickinson Canto II or an LSRII and analyzed using FlowJo v10 (Treestar). FlowJosuggested: (FlowJo, RRID:SCR_008520)Data were analyzed using Prism (Graphpad). Prismsuggested: (PRISM, RRID:SCR_005375)Graphpadsuggested: (GraphPad, RRID:SCR_000306)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:A limitation of our study is that we only performed adoptive sera transfers early after nucleocapsid vaccination. It is unknown if a similar level of protection would be observed if the passive immunizations were performed using sera from later time points post-vaccination. We detected memory B cells, suggesting that the nucleocapsid-specific antibody response was long-lived, but future studies are needed to evaluate the durability of nucleocapsid-specific antibody responses and the mechanisms by which they clear SARS-CoV-2 infection. Overall, we show that passive immunization using nucleocapsid-specific sera improves the control of a SARS-CoV-2 infection. These data provide insights for next-generation vaccines and for expanding the armamentarium of antibody-based therapies for COVID-19.
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.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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