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Published on: February 16, 2022
SARS-CoV-2 antibody responses in children exhibit higher FcR engagement and avidity than in adults
Carolyn A Cohen1, Ludivine Grzelak2, Susan S Chiu3
1HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Insights
Children mount a distinct SARS-CoV-2 antibody response compared to adults, generating more targeted and functional antibodies. This difference in humoral immunity highlights unique pediatric immune system characteristics in fighting the virus.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Intrinsic differences in humoral immune responses to SARS-CoV-2 between children and adults are not well understood.
- Understanding these differences is crucial for assessing pediatric vulnerability and immune protection against SARS-CoV-2.
Purpose of the Study:
- To characterize and compare the kinetics, specificity, and function of SARS-CoV-2 antibodies in children versus adults.
- To elucidate the distinct immunological profiles of pediatric and adult humoral immunity following SARS-CoV-2 infection.
Main Methods:
- Analysis of plasma samples from a cohort of infection and vaccination-naive children and adults with confirmed SARS-CoV-2 (ancestral B.1* strain) infection.
- Assessment of antibody responses from acute to convalescent phases, including antibody levels, isotype switching, avidity, and Fc receptor (FcR)-binding functionality.
- Comparison of antibody characteristics against SARS-CoV-2 Spike and Nucleocapsid proteins, as well as common cold coronavirus antigens.
Main Results:
- Children exhibited significantly lower overall primary antibody responses and less isotype switching compared to adults.
- Children showed lower IgG and avidity for OC43 Spike and SARS-CoV-2 S2 but higher avidity for whole SARS-CoV-2 Spike and Nucleocapsid.
- Children demonstrated higher levels of Spike FcγR-binding antibodies, suggesting a more targeted and functional de novo immune response.
Conclusions:
- Adult SARS-CoV-2 antibody responses may be influenced by pre-existing cross-reactive immunity to common cold coronaviruses.
- Children generate de novo SARS-CoV-2-specific Spike and Nucleocapsid IgG with robust FcR binding and high avidity, indicating a more targeted and functional response.
- These findings highlight distinct pediatric humoral immune strategies against SARS-CoV-2, emphasizing targeted and functional antibody generation.
Abstract:
As intrinsic differences in humoral immune response to SARS-CoV-2 between children and adults remain unclear, we improved characterisation by defining the kinetics, specificity and function of antibodies to SARS-CoV-2 in children (n = 146, aged 9.4 ± 4.8 years with n = 257 samples) compared to adults (n = 85, aged 39.5 ± 15.2 years with n = 122 samples). We used plasma samples from an infection and vaccination-naive cohort study with RT-PCR confirmed ancestral B.1* SARS-CoV-2 virus infection with asymptomatic or mild disease, collected in Hong Kong between March to December 2020, from acute (0-14 days post infection) to convalescent (15-206 days) timepoints. Children had significantly lower primary antibody responses against SARS-CoV-2 proteins overall, leading to a less isotype switched response. While children had lower OC43 Spike and SARS-CoV-2 S2 IgG and avidity than adults, they exhibited higher avidities for SARS-CoV-2 whole Spike and Nucleocapsid, and higher levels of Spike FcγR-binding antibodies. Adults' SARS-CoV-2 antibody responses could be derived from high avidity pre-existing cross-reactive common cold coronavirus B cell responses, whilst children appear to generate a de novo SARS-CoV-2- specific Spike and Nucleocapsid IgG with robust Fc receptor (FcR) binding ability and high avidity at a higher proportion than adults, thus their responses are more targeted and functional for SARS-CoV-2.
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