key: cord-0700581-hc72iku3
authors: Kardava, Lela; Rachmaninoff, Nicholas; Lau, William W.; Buckner, Clarisa M.; Trihemasava, Krittin; de Assis, Felipe Lopes; Wang, Wei; Zhang, Xiaozhen; Wang, Yimeng; Chiang, Chi-I; Narpala, Sandeep; Reger, Robert; McCormack, Genevieve E.; Seamon, Catherine A.; Childs, Richard W.; Suffredini, Anthony F.; Strich, Jeffrey R.; Chertow, Daniel S.; Davey, Richard T.; Sneller, Michael C.; O’Connell, Sarah; Li, Yuxing; McDermott, Adrian; Chun, Tae-Wook; Fauci, Anthony S.; Tsang, John S.; Moir, Susan
title: Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine
date: 2021-07-07
journal: medRxiv
DOI: 10.1101/2021.07.06.21259528
sha: b43d15216601ee22dbee66bf5b9ecb823ff586c2
doc_id: 700581
cord_uid: hc72iku3

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.

Correlations between serum IgG and IgA binding to RBD (Fig. 1b) and ACE2 inhibition assay 7 ( Fig. 1e ) with v2 timepoints shown with color-coding (top panel) or exclusively measurements at 8 v2D28 (lower panel). b, Longitudinal frequencies of RBD + S1 + PB and IgG + B cells vaccinees (n 9 = 21) color-coded as in Fig. 1 . c, Binding by flow cytometry of S-2P, S1 and RBD tetramers to 10 PB and IgG + B cells of an individual at v2D6. d, Correlation between flow cytometric and 11

ELISpot assays measuring frequencies of RBD + and S1 + PB at peak dose 1 and 2 post mRNA- 

Extended Data Table 4: COVID-19 patient information 51