BNT162b2-induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 diminish with age

Bates, Timothy A.; Lu, Pei; Kang, Ye jin; Schoen, Devin; Thornton, Micah; McBride, Savannah K.; Park, Chanhee; Kim, Dae-Hwan; Messer, William B.; Curlin, Marcel E.; Tafesse, Fikadu G.; Lu, Lenette L.

doi:10.1016/j.celrep.2022.111544

Cited by 29 publications

(51 citation statements)

References 91 publications

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“…Despite the diminished neutralizing ability of vaccine-elicited antibodies against SARS-CoV-2 variants with amino acid substitutions in the RBD and NTD 9,16 , protection against severe disease is maintained in the majority of vaccine recipients 28,29 . Although neutralizing activity of antibodies is a correlate of vaccine-mediated protection 3 , the ability of monovalent COVID-19 vaccines to limit Omicron disease in the setting of waning serum antibody neutralization suggests additional protective immune mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…https://doi.org/10.1038/s41564-023-01359-1 protein avidly enough to trigger Fc effector functions retain protective activity 11,15 . Analogously, non-neutralizing antibodies induced by SARS-CoV-2 vaccines have been linked to protection against variant Omicron strains by virtue of their ability to engage FcγRs and promote clearance 16,17 . Furthermore, the depletion of RBD-specific antibodies from serum of mRNA-1273 or BNT162b2 vaccinated individuals did not appreciably impact Fc-mediated effector function activity in cell culture 4 , suggesting that antibodies recognizing conserved, non-neutralizing epitopes may contribute to protection against variant strains.…”

Section: Articlementioning

confidence: 99%

See 1 more Smart Citation

Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2

et al. 2023

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Extended Data Fig. 1 | Gating strategy for Luminex-based and Fc effector function assays. (a) Gating for Luminex-bead based antibody binding to spike-coated beads. (b) Gating for ADNP assay showing CD66 + neutrophils with opsinophagocytosed beads. (c) Gating for ADCP assay showing THP-1 monocytes and opsinophagocytosed beads. (d) Gating for ADCD assay showing complement deposition on spike and antibody coated beads. (e) Gating for NK cell activation assay showing CD107a expression.

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Section: Discussionmentioning

confidence: 99%

Section: Articlementioning

confidence: 99%

Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2

et al. 2023

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show abstract

“…Despite the diminished neutralizing ability of vaccine-elicited antibodies against SARS-CoV-2 variants with amino acid substitutions in the RBD and NTD 12,21 , protection against severe disease is maintained in the majority of vaccine recipients 36,37 . Although neutralizing activity of antibodies is a correlate of vaccine-mediated protection 4 , the ability of monovalent COVID-19 vaccines to protect against Omicron disease in the setting of waning serum antibody neutralization suggests additional protective immune mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, monoclonal antibodies (mAbs) that lose their ability to neutralize SARS-CoV-2 variants yet still bind the spike protein avidly enough to trigger Fc effector functions retain protective activity 15,20 . Analogously, non-neutralizing antibodies induced by SARS-CoV-2 vaccines have been linked to protection against variant Omicron strains by virtue of their ability to engage FcγRs and promote clearance [21][22][23] . Furthermore, the depletion of RBDspecific antibodies from serum of mRNA-1273 or BNT162b2 vaccinated individuals did not appreciably impact Fc-mediated effector function activity in cell culture 6 , suggesting that antibodies recognizing conserved, non-neutralizing epitopes may contribute to protection against variant strains.…”

Section: Introductionmentioning

confidence: 99%

Fcγ receptor-dependent antibody effector functions are required for vaccine protection against infection by antigenic variants of SARS-CoV-2

Mackin

Desai

Whitener

et al. 2022

Preprint

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Emerging SARS-CoV-2 variants with antigenic changes in the spike protein are neutralized less efficiently by serum antibodies elicited by legacy vaccines against the ancestral Wuhan-1 virus. Nonetheless, these vaccines, including mRNA-1273 and BNT162b2, retained their ability to protect against severe disease and death, suggesting that other aspects of immunity control infection in the lung. Although vaccine-elicited antibodies can bind Fc gamma receptors and mediate effector functions against SARS-CoV-2 variants, and this property correlates with improved clinical COVID-19 outcome, a causal relationship between Fc effector functions and vaccine-mediated protection against infection has not been established. Here, using passive and active immunization approaches in wild-type and Fc-gamma receptor (FcgR) KO mice, we determined the requirement for Fc effector functions to protect against SARS-CoV-2 infection. The antiviral activity of passively transferred immune serum was lost against multiple SARS-CoV-2 strains in mice lacking expression of activating FcgRs, especially murine FcgR III (CD16), or depleted of alveolar macrophages. After immunization with the preclinical mRNA-1273 vaccine, protection against Omicron BA.5 infection in the respiratory tract also was lost in mice lacking FcgR III. Our passive and active immunization studies in mice suggest that Fc-FcgR engagement and alveolar macrophages are required for vaccine-induced antibody-mediated protection against infection by antigenically changed SARS-CoV-2 variants, including Omicron strains.

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“…If we understand the spectrum of IgG-mediated functions in the fetus then we can design ways to leverage maternal immunity to protect the infant. SARS-CoV-2 mRNA vaccines and infection generate IgG with neutralizing and antibody Fc effector functions in the non-pregnant (26)(27)(28)(29) and pregnant populations (30)(31)(32)(33)(34)(35). With Fc-Fc receptor engagement on innate and adaptive immune cells (36,37), induced effector functions can prevent disease even after infection has occurred by eliminating infected cells and blocking spread (25,(38)(39)(40)(41)(42)(43)(44).…”

Section: Introductionmentioning

confidence: 99%

Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy

Adhikari

Kang

et al. 2023

Preprint

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Immunization in pregnancy is a critical tool that can be leveraged to protect the infant with an immature immune system but how vaccine-induced antibodies transfer to the placenta and protect the maternal-fetal dyad remains unclear. Here, we compare matched maternal-infant cord blood from individuals who in pregnancy received mRNA COVID-19 vaccine, were infected by SARS-CoV-2, or had the combination of these two immune exposures. We find that some but not all antibody neutralizing activities and Fc effector functions are enriched with vaccination compared to infection. Preferential transport to the fetus of Fc functions and not neutralization is observed. Immunization compared to infection enriches IgG1-mediated antibody functions with changes in antibody post-translational sialylation and fucosylation that impact fetal more than maternal antibody functional potency. Thus, vaccine enhanced antibody functional magnitude, potency and breadth in the fetus are driven more by antibody glycosylation and Fc effector functions compared to maternal responses, highlighting prenatal opportunities to safeguard newborns as SARS-CoV-2 becomes endemic.

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BNT162b2-induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 diminish with age

Cited by 29 publications

References 91 publications

Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2

Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2

Fcγ receptor-dependent antibody effector functions are required for vaccine protection against infection by antigenic variants of SARS-CoV-2

Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy

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