Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect In Vivo in a Mouse Model in a Neutralization-Dependent Manner
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Abstract
Cross-neutralization of SARS-CoV-2 variants by RBD-targeting antibodies is still not well understood, and very little is known about the potential protective effect of nonneutralizing antibodies in vivo . Using a panel of mouse monoclonal antibodies, we investigate both of these points.
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SciScore for 10.1101/2021.04.05.438547: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Generation of monoclonal antibodies: All animal work was performed by adhering to institutional regulation as well as Institutional Animal Care and Use Committee (IACUC) guidelines. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Six to eight weeks old, female, mice (Jackson Laboratories) were immunized with 3 ugs of purified RBD of SARS-CoV-2 mixed with 10 ugs of poly I:C (Invivogen) twice with 3 weeks interval (17, 29). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The virus stock was titered in Vero.E6 cells as well. Vero.E6suggested: JCRB Cat# …SciScore for 10.1101/2021.04.05.438547: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Generation of monoclonal antibodies: All animal work was performed by adhering to institutional regulation as well as Institutional Animal Care and Use Committee (IACUC) guidelines. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Six to eight weeks old, female, mice (Jackson Laboratories) were immunized with 3 ugs of purified RBD of SARS-CoV-2 mixed with 10 ugs of poly I:C (Invivogen) twice with 3 weeks interval (17, 29). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources The virus stock was titered in Vero.E6 cells as well. Vero.E6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)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:However, there is an important caveat that needs to be discussed for this experiment. All non-neutralizing antibodies that we isolated were of the IgG1 subtype, which in mice, is known to have low affinity for activating FcRs. This is in contrast to murine IgG2a and IgG2b which have high affinity for these FcRs. Therefore, we can only conclude that non-Fc-FcR based interactions do not contribute to protection by non-neutralizing antibodies. In fact, the two antibodies that provided the best protection, especially on day 3, KL-S-1D2 and KL-S-2C3, are both of the IgG2a subtype. While KL-S-1D2 showed the best in vitro neutralization of all isolated mAbs, which could cause this phenotype, KL-S-2C3’s in vitro activity was lower but still showed stronger activity in vivo than other mAbs. This could be seen as evidence that Fc-FcR interactions, especially engagement with activating FcRs, which is an important component of protection. Of note, the vast majority of antibodies induced in humans to SARS-CoV-2 spike by natural infection or vaccination are IgG1 and in humans – unlike in mice - IgG1 has strong affinity for activating FcRs (29). In summary, we describe several antibodies to the SARS-CoV-2 RBD that maintain strong neutralizing activity against the B.1.1.7 as well as B.1.351 variant. These mAbs, if humanized, may be further developed into ‘variant resistant’ therapeutics.
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:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
- 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.
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