Non-neutralizing functions in anti-SARS-CoV-2 IgG antibodies

Reinig, Sebastian; Shih, Shin-Ru

doi:10.1016/j.bj.2023.100666

Cited by 3 publications

(5 citation statements)

References 98 publications

(162 reference statements)

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“…The previous study normalized the samples to the IgG concentration, whereas the samples were normalized to the plasma volume in this study, which is more commonly used [20][21][22] and is representative of the overall humoral immune response. Furthermore, normalization of the antigenic IgG concentration is more suitable for antibody therapies in which the applied antibody concentration can be controlled; however, ADCP decline may indicate a weakening of antibody-mediated protection since ADCP and ADCC are potential protective mechanisms of Fc-mediated functions against viruses 23 .…”

Section: Discussionmentioning

confidence: 99%

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Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines

Reinig

Kuo

et al. 2023

Preprint

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Different vaccine platforms were developed in 2019 and 2020 to provide immunization for protection against the SARS-CoV-2-caused disease COVID-19. The majority of vaccinated individuals will develop antibodies against SARS-CoV-2. The isotype (subclass) and Fc-glycosylation of IgG antibodies determine their affinity for secondary effector functions. For protein subunit vaccines in COVID-19, the IgG profile of the subclass and glycosylation are unknown. Therefore, we measured the IgG subclass and N-297 Fc glycosylation by ELISA and LC-MS/MS of anti-spike IgG from individuals vaccinated with the Taiwanese protein subunit vaccine Medigen, the mRNA vaccines (BNT, Moderna), and the adenovector Astrazeneca. Samples were taken after the first and second doses. For all vaccine types, the main IgG response was dominated by IgG1 and IgG3 as subclasses. For glycosylation, mRNA vaccines presented with an afucosylation after the first dose and a constant significant higher galactosylation and sialylation than non-mRNA vaccines.

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Section: Discussionmentioning

confidence: 99%

“…The complement system has no potential protective role in viral or SARS-CoV-2 infection, and overactivation of the complement system may be harmful 23 . No adverse reactions were reported in the three-dose Medigen-vaccinated population if these individuals were infected with SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines

Reinig

Kuo

et al. 2023

Preprint

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“…4 Fc-mediated functions are potentially the primary mechanisms by which IgG antibodies are activated against the SARS-CoV-2 virus. 5 The affinity of IgG for Fc-mediated functions is determined by the isotype (subclass) and the conserved n-297 glycosylation site. 6,7 Several studies have investigated the long-term changes in the IgG profile of mRNA vaccines, showing an increased contribution of the IgG4 subclass of anti-S IgG 8-10 associated with weaker Fc-mediated functions.…”

Section: Introductionmentioning

confidence: 99%

“…IgG can also bind to Fc receptors and activate the innate immune effector via its Fc domain, including antibody‐dependent‐cellular phagocytosis (ADCP), cellular cytotoxicity (ADCC), and complement deposition (ADCD) 4 . Fc‐mediated functions are potentially the primary mechanisms by which IgG antibodies are activated against the SARS‐CoV‐2 virus 5 . The affinity of IgG for Fc‐mediated functions is determined by the isotype (subclass) and the conserved n‐297 glycosylation site 6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…The previous study normalized the samples to the IgG concentration, whereas the samples were normalized to the plasma volume in this study, which is more commonly used[24][25][26] and is representative of the overall humoral immune response. Furthermore, normalization of the antigenic IgG concentration is more suitable for antibody therapies in which the applied antibody concentration can be controlled; however, ADCP decline may indicate a weakening of antibody-mediated protection since ADCP and ADCC are potential protective mechanisms of Fcmediated functions against viruses 5.…”

mentioning

confidence: 99%

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Specific long‐term changes in anti‐SARS‐CoV‐2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines

Reinig,

Kuo,

et al. 2024

Journal of Medical Virology

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Various vaccine platforms were developed and deployed against the COVID‐19 disease. The Fc‐mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long‐term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme‐linked immunosorbent assay, and Fc‐N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody‐dependent‐cellular‐phagocytosis (ADCP) and complement deposition (ADCD) of anti‐spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti‐S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA‐ and Medigen‐vaccinated individuals. Fc‐glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti‐S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca‐vaccinated individuals. Each vaccine produced specific long‐term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.

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Evolutionary edge: NOD-like receptors in immunity

Kattner

2024

Biomedical Journal

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Non-neutralizing functions in anti-SARS-CoV-2 IgG antibodies

Cited by 3 publications

References 98 publications

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines

Specific long‐term changes in anti‐SARS‐CoV‐2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines

Evolutionary edge: NOD-like receptors in immunity

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