Dataset Information

Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity.

ABSTRACT: The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. The carbohydrates on the RBD proteins were enzymatically modulated, and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. Removal of all carbohydrates diminished antibody reactivity, while removal of only sialic acids or terminal fucoses improved the reactivity. The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity, verifying the importance of these specific monosaccharides. The results can be of importance for the design of future vaccine candidates, indicating that it is possible to enhance the immunogenicity of recombinant viral proteins.

SUBMITTER: Samuelsson E

PROVIDER: S-EPMC9469093 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity.

Samuelsson Ebba E Mirgorodskaya Ekaterina E Nyström Kristina K Bäckström Malin M Liljeqvist Jan-Åke JÅ Nordén Rickard R

ACS infectious diseases 20220818 9

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. We defined the carbohydrate content of the recombinant RBD produced in different mammalian cells. We found a higher degree of complex-type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. The carbohydrates on the RBD proteins we ...[more]

PMID: 35980012

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Project description:Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020-August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.

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Dataset Information

Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity.

Publications

Sialic Acid and Fucose Residues on the SARS-CoV-2 Receptor-Binding Domain Modulate IgG Antibody Reactivity.

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