tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2024 Jan 16;121(3):e2314730121.
doi: 10.1073/pnas.2314730121. Epub 2024 Jan 10. High-resolution map of the Fc functions mediated by COVID-19-neutralizing antibodies
Ida Paciello[SUP] 1 [/SUP], Giuseppe Maccari[SUP] 2 [/SUP], Elisa Pantano[SUP] 1 [/SUP], Emanuele Andreano[SUP] 1 [/SUP], Rino Rappuoli[SUP] 3 4 [/SUP]
Affiliations
A growing body of evidence shows that fragment crystallizable (Fc)-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc functions. Surprisingly, we found that nAbs with the most potent Fc function recognize the N-terminal domain, followed by those targeting class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc functions. The divergent properties of the neutralizing and Fc function-mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc functions of polyclonal sera differ from the profile observed with nAbs, suggesting that non-neutralizing antibodies also contribute to Fc functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies, and the evaluation of correlates of protection.
Keywords: B cell germlines; Fc function; SARS-CoV-2; antibodies.
. 2024 Jan 16;121(3):e2314730121.
doi: 10.1073/pnas.2314730121. Epub 2024 Jan 10. High-resolution map of the Fc functions mediated by COVID-19-neutralizing antibodies
Ida Paciello[SUP] 1 [/SUP], Giuseppe Maccari[SUP] 2 [/SUP], Elisa Pantano[SUP] 1 [/SUP], Emanuele Andreano[SUP] 1 [/SUP], Rino Rappuoli[SUP] 3 4 [/SUP]
Affiliations
- PMID: 38198525
- DOI: 10.1073/pnas.2314730121
A growing body of evidence shows that fragment crystallizable (Fc)-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc functions. Surprisingly, we found that nAbs with the most potent Fc function recognize the N-terminal domain, followed by those targeting class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc functions. The divergent properties of the neutralizing and Fc function-mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc functions of polyclonal sera differ from the profile observed with nAbs, suggesting that non-neutralizing antibodies also contribute to Fc functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies, and the evaluation of correlates of protection.
Keywords: B cell germlines; Fc function; SARS-CoV-2; antibodies.