Caitlin I. Stoddard1, Kevin Sung2, Zak A. Yaffe1,3, Haidyn Weight1, Guillaume Beaudoin-Bussières4,5, Jared Galloway2, Soren Gantt5,6, Judith Adhiambo7, Emily R. Begnel8, Ednah Ojee7, Jennifer Slyker8, Dalton Wamalwa7, John Kinuthia8,9, Andrés Finzi4,5, Frederick A. Matsen IV2,10, Dara A. Lehman1,8*, Julie Overbaugh1,2,11*
1Human Biology Division, Fred Hutchinson Cancer Center
2Public Health Sciences Division, Fred Hutchinson Cancer Center
3Medical Scientist Training Program, University of Washington
4Centre de Recherche du CHUM, Université de Montréal
5Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal
6Centre de Recherche du CHU Sainte-Justine, Université de Montréal
7Department of Pediatrics and Child Health, University of Nairobi
8Department of Global Health, University of Washington
9Department of Research and Programs, Kenyatta National Hospital
10Howard Hughes Medical Institute
11Lead contact
*Correspondence
Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. We characterized antibody binding and functionality in convalescent plasma from postpartum women and their infants infected with SARS-CoV-2 from a vaccine-naïve prospective cohort in Nairobi, Kenya. Antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels were significantly higher in infants than in mothers. Plasma antibodies from mothers and infants bound to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants displayed higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants had significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, neutralization titers between infants and mothers were similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody activities and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.
The Phage-DMS data after alignment pipeline processing, replicate selection, and calculation of enrichments and scaled differential selection, is provided in LK_DMS_1rep_layered.phip. The code for downstream analyses and generation of plots for some figures in the manuscript is provided here. Outputs from the Jupyter notebooks are saved to the results/ directory.
Currently, the environment is set up with Conda and pip. Clone this repository and create the lk-sars2-env environment as follows:
git clone https://github.com/matsengrp/LK-SARS-CoV-2
cd LK-SARS-CoV-2
conda env create -f environment.yml
conda activate lk-sars2-env
pip install logomaker
git clone https://github.com/matsengrp/phippery
cd phippery
git checkout 3c680c3
pip install .
cd -The wildtype enrichments heatmap of Fig. 2A, and the summed enrichment data for Fig. 2B and Fig. 2C are generated with PhIP_wt_analysis.ipynb.
The logo plots and and box plots of scaled differential selection in Figs. 3A, 3B, 4A, 4B, S4, and S5 are generated with DMS_logo_diff_sel.ipynb. The average similarity data in Figs. 3C and 4C are generated with DMS_avg_sim_profile.ipynb. The pairwise similarity data in Figs. 3D and 4D are generated with DMS_escape_compare_sims.ipynb.
The eigenassay plots from principal component analysis is generated with PhIP_pca.ipynb.
The raw sequencing data was processed using phip-flow and phippery software tools. See here for detailed documentation. For questions related to processing the Phage-DMS data for this manuscript, please contact Kevin Sung: ksung2 (at) fredhutch (dot) org.