Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers
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 characte...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40554-w |
| _version_ | 1797558708694155264 |
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| author | 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 Julie Overbaugh |
| author_facet | 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 Julie Overbaugh |
| author_sort | Caitlin I. Stoddard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:34:50Z |
| format | Article |
| id | doaj.art-381205a79ec3443fa2094048529a97e1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:34:50Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-381205a79ec3443fa2094048529a97e12023-11-20T09:53:28ZengNature PortfolioNature Communications2041-17232023-08-0114111210.1038/s41467-023-40554-wElevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothersCaitlin I. Stoddard0Kevin Sung1Zak A. Yaffe2Haidyn Weight3Guillaume Beaudoin-Bussières4Jared Galloway5Soren Gantt6Judith Adhiambo7Emily R. Begnel8Ednah Ojee9Jennifer Slyker10Dalton Wamalwa11John Kinuthia12Andrés Finzi13Frederick A. Matsen14Dara A. Lehman15Julie Overbaugh16Human Biology Division, Fred Hutchinson Cancer CenterPublic Health Sciences Division, Fred Hutchinson Cancer CenterHuman Biology Division, Fred Hutchinson Cancer CenterHuman Biology Division, Fred Hutchinson Cancer CenterCentre de Recherche du CHUM, Université de MontréalPublic Health Sciences Division, Fred Hutchinson Cancer CenterDépartement de Microbiologie, Infectiologie et Immunologie, Université de MontréalDepartment of Pediatrics and Child Health, University of NairobiDepartment of Global Health, University of WashingtonDepartment of Pediatrics and Child Health, University of NairobiDepartment of Global Health, University of WashingtonDepartment of Pediatrics and Child Health, University of NairobiDepartment of Global Health, University of WashingtonCentre de Recherche du CHUM, Université de MontréalPublic Health Sciences Division, Fred Hutchinson Cancer CenterHuman Biology Division, Fred Hutchinson Cancer CenterHuman Biology Division, Fred Hutchinson Cancer CenterAbstract 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.https://doi.org/10.1038/s41467-023-40554-w |
| spellingShingle | 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 Julie Overbaugh Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers Nature Communications |
| title | Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers |
| title_full | Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers |
| title_fullStr | Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers |
| title_full_unstemmed | Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers |
| title_short | Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers |
| title_sort | elevated binding and functional antibody responses to sars cov 2 in infants versus mothers |
| url | https://doi.org/10.1038/s41467-023-40554-w |
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