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[Preprint]. 2021 Mar 24:2021.03.24.436864.
doi: 10.1101/2021.03.24.436864.

A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

Aaron J Schmitz  1 , Jackson S Turner  1 , Zhuoming Liu  2 , Ishmael D Aziati  3 , Rita E Chen  1   3 , Astha Joshi  3 , Traci L Bricker  3 , Tamarand L Darling  3 , Daniel C Adelsberg  4 , Wafaa B Alsoussi  1   2 , James Brett Case  3 , Tingting Lei  1 , Mahima Thapa  1 , Fatima Amanat  4   5 , Jane A O'Halloran  3 , Pei-Yong Shi  6 , Rachel M Presti  3 , Florian Krammer  4 , Goran Bajic  4 , Sean P J Whelan  2 , Michael S Diamond  1   2   3   7 , Adrianus C M Boon  1   2   3 , Ali H Ellebedy  1   2   7
Affiliations

A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

Aaron J Schmitz et al. bioRxiv. .

Update in

  • A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants.
    Schmitz AJ, Turner JS, Liu Z, Zhou JQ, Aziati ID, Chen RE, Joshi A, Bricker TL, Darling TL, Adelsberg DC, Altomare CG, Alsoussi WB, Case JB, VanBlargan LA, Lei T, Thapa M, Amanat F, Jeevan T, Fabrizio T, O'Halloran JA, Shi PY, Presti RM, Webby RJ, Krammer F, Whelan SPJ, Bajic G, Diamond MS, Boon ACM, Ellebedy AH. Schmitz AJ, et al. Immunity. 2021 Sep 14;54(9):2159-2166.e6. doi: 10.1016/j.immuni.2021.08.013. Epub 2021 Aug 17. Immunity. 2021. PMID: 34464596 Free PMC article.

Abstract

The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.

One sentence summary: Protection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.

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Figures

Figure 1.
Figure 1.. mAb 2C08 potently neutralizes diverse SARS-CoV-2 strains.
(A and B) ELISA binding to recombinant RBD from (A) and neutralizing activity in Vero-TMPRSS2 cells against (B) indicated SARS-CoV-2 strains by the indicated mAbs. ELISA binding to D614G RBD previously reported in (29). Baseline for area under the curve was set to the mean + three times the standard deviation of background binding to bovine serum albumin. Dotted lines indicate limit of detection. Bars indicate mean ± SEM. Results are from one experiment performed in duplicate (panel A, D614G) or in singlet (panel A, B.1.1.7, B.1.351, and B.1.1.248), or two experiments performed in duplicate (panel B).
Figure 2.
Figure 2.. mAb 2C08 protects hamsters from SARS-CoV-2 challenge.
(A–D) Percent weight change (A), lung viral RNA titer (B), lung infectious virus titer (C), and lung cytokine gene expression (D) of hamsters that received isotype (black) or 2C08 (grey) one day prior to intranasal challenge with 5×105 PFU D614G (left) or B.1.351 (right) SARS-CoV-2. In (A), symbols indicate mean ± SEM. In (B and C), bars indicate geometric mean ± geometric SD, and each symbol represents one hamster. In (D), bars indicate mean ± SD, and each symbol represents one hamster. Data are from one experiment, n = 5 per condition. P-values from two-tailed Mann-Whitney tests (A–C) and unpaired two-tailed t-tests (D).
Figure 3.
Figure 3.. mAb 2C08 recognizes a public epitope in SARS-CoV-2 RBD.
(A) Plaque assay on Vero cells with no antibody (left) or 2C08 (right) in the overlay to isolate escape mutants (red arrow). Data are representative of three experiments. (B) Structure of RBD (from PDB 6M0J) with hACE2 footprint highlighted in magenta and amino acids whose substitution confers resistance to 2C08 in plaque assays highlighted in yellow. (C) Sequence alignment of 2C08 with RBD-binding mAbs from SARS-CoV-2 infected patients and vaccinees that utilize the same immunoglobulin heavy and light chain variable region genes (see also Table S1). Stars indicate contact residues.
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References

    1. Chan J. F.-W., Yuan S., Kok K.-H., To K. K.-W., Chu H., Yang J., Xing F., Liu J., Yip C. C.-Y., Poon R. W.-S., Tsoi H.-W., Lo S. K.-F., Chan K.-H., Poon V. K.-M., Chan W.-M., Ip J. D., Cai J.-P., Cheng V. C.-C., Chen H., Hui C. K.-M., Yuen K.-Y., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 395, 514–523 (2020). - PMC - PubMed
    1. Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y., Ren R., Leung K. S. M., Lau E. H. Y., Wong J. Y., Xing X., Xiang N., Wu Y., Li C., Chen Q., Li D., Liu T., Zhao J., Liu M., Tu W., Chen C., Jin L., Yang R., Wang Q., Zhou S., Wang R., Liu H., Luo Y., Liu Y., Shao G., Li H., Tao Z., Yang Y., Deng Z., Liu B., Ma Z., Zhang Y., Shi G., Lam T. T. Y., Wu J. T., Gao G. F., Cowling B. J., Yang B., Leung G. M., Feng Z., Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. N. Engl. J. Med. 382, 1199–1207 (2020). - PMC - PubMed
    1. WHO COVID-19 Dashboard (2020), (available at https://covid19.who.int/).
    1. FDA, Recommendations for Investigational COVID-19 Convalescent Plasma, (available at https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-in...).
    1. Krammer F., SARS-CoV-2 vaccines in development. Nature. 586, 516–527 (2020). - PubMed

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