Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers

Caitlin I. Stoddard, Kevin Sung, Zak A. Yaffe, Haidyn Weight, Guillaume Beaudoin-Bussières, Jared Galloway, Soren Gantt, Judith Adhiambo, Emily R. Begnel, Ednah Ojee, Jennifer Slyker, Dalton Wamalwa, John Kinuthia, Andrés Finzi, Frederick A. Matsen, Dara A. Lehman () and Julie Overbaugh ()
Additional contact information
Caitlin I. Stoddard: Fred Hutchinson Cancer Center
Kevin Sung: Fred Hutchinson Cancer Center
Zak A. Yaffe: Fred Hutchinson Cancer Center
Haidyn Weight: Fred Hutchinson Cancer Center
Guillaume Beaudoin-Bussières: Université de Montréal
Jared Galloway: Fred Hutchinson Cancer Center
Soren Gantt: Université de Montréal
Judith Adhiambo: University of Nairobi
Emily R. Begnel: University of Washington
Ednah Ojee: University of Nairobi
Jennifer Slyker: University of Washington
Dalton Wamalwa: University of Nairobi
John Kinuthia: University of Washington
Andrés Finzi: Université de Montréal
Frederick A. Matsen: Fred Hutchinson Cancer Center
Dara A. Lehman: Fred Hutchinson Cancer Center
Julie Overbaugh: Fred Hutchinson Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract 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. Here, we characterize antibody binding and functionality against Wuhan-Hu-1 (B lineage) strain SARS-CoV-2 in convalescent plasma from 36 postpartum women and 14 of their infants infected with SARS-CoV-2 from a vaccine-naïve prospective cohort in Nairobi, Kenya. We find significantly higher antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels in infants versus mothers. Plasma antibodies from mothers and infants bind to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants display higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants have significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, Spike pseudovirus neutralization titers between infants and mothers are 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.

Date: 2023
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DOI: 10.1038/s41467-023-40554-w

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