Anamnestic humoral correlates of immunity across SARS-CoV-2 variants of concern.

Autor:	McNamara RP; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA., Maron JS; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA., Boucau J; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA., Roy V; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA., Webb NE; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA., Bertera HL; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA., Barczak AK; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA.; Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts, USA.; Harvard Medical School , Boston, Massachusetts, USA., Positives Study Staff T; Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts, USA.; Department of Medicine, Brigham and Women's Hospital , Boston, Massachusetts, USA., Franko N; Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington, USA., Logue JK; Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington, USA., Kemp M; Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington, USA., Li JZ; Harvard Medical School , Boston, Massachusetts, USA.; Department of Medicine, Brigham and Women's Hospital , Boston, Massachusetts, USA., Zhou L; Department of Molecular Biosciences, University of Texas at Austin , Austin, Texas, USA., Hsieh CL; Department of Molecular Biosciences, University of Texas at Austin , Austin, Texas, USA., McLellan JS; Department of Molecular Biosciences, University of Texas at Austin , Austin, Texas, USA., Siedner MJ; Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts, USA.; Harvard Medical School , Boston, Massachusetts, USA., Seaman MS; Harvard Medical School , Boston, Massachusetts, USA.; Beth Israel Deaconess Medical Center , Boston, Massachusetts, USA., Lemieux JE; Department of Medicine, Massachusetts General Hospital , Boston, Massachusetts, USA.; Harvard Medical School , Boston, Massachusetts, USA.; The Broad Institute , Cambridge, Massachusetts, USA., Chu HY; Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington, USA., Alter G; Ragon Institute of MGH, MIT, and Harvard , Cambridge, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2023 Aug 31; Vol. 14 (4), pp. e0090223. Date of Electronic Publication: 2023 Aug 03.
DOI:	10.1128/mbio.00902-23
Abstrakt:	While immune correlates against SARS-CoV-2 are typically defined at peak immunogenicity following vaccination, immunologic responses that expand selectively during the anamnestic response following infection can provide mechanistic and detailed insights into the immune mechanisms of protection. Moreover, whether anamnestic correlates are conserved across variants of concern (VOC), including the Delta and more distant Omicron VOC, remains unclear. To define the anamnestic correlates of immunity, across VOCs, we deeply profiled the humoral immune response in individuals infected with sequence-confirmed Delta or Omicron VOC after completing the vaccination series. While limited acute N-terminal domain and receptor-binding domain (RBD)-specific immune expansion was observed following breakthrough infection, a significant immunodominant expansion of opsonophagocytic Spike-specific antibody responses focused largely on the conserved S2-domain of SARS-CoV-2 was observed. This S2-specific functional humoral response continued to evolve over 2-3 weeks following Delta or Omicron breakthrough, targeting multiple VOCs and common coronaviruses. Strong responses were observed on the fusion peptide (FP) region and the heptad repeat 1 (HR1) region adjacent to the RBD. Notably, the FP is highly conserved across SARS-related coronaviruses and even non-SARS-related betacoronavirus. Taken together, our results point to a critical role of highly conserved, functional S2-specific responses in the anamnestic antibody response to SARS-CoV-2 infection across VOCs. These humoral responses linked to virus clearance can guide next-generation vaccine-boosting approaches to confer broad protection against future SARS-related coronaviruses. IMPORTANCE The Spike protein of SARS-CoV-2 is the primary target of antibody-based recognition. Selective pressures, be it the adaption to human-to-human transmission or evasion of previously acquired immunity, have spurred the emergence of variants of the virus such as the Delta and Omicron lineages. Therefore, understanding how antibody responses are expanded in breakthrough cases of previously vaccinated individuals can provide insights into key correlates of protection against current and future variants. Here, we show that vaccinated individuals who had documented COVID-19 breakthrough showed anamnestic antibody expansions targeting the conserved S2 subdomain of Spike, particularly within the fusion peptide region. These S2-directed antibodies were highly leveraged for non-neutralizing, phagocytic functions and were similarly expanded independent of the variant. We propose that through deep profiling of anamnestic antibody responses in breakthrough cases, we can identify antigen targets susceptible to novel monoclonal antibody therapy or vaccination-boosting strategies. Competing Interests: Galit Alter is a founder/equity holder in Seromyx Systems and Leyden Labs. G.A. has served as a scientific advisor for Sanofi Vaccines. G.A. has collaborative agreements with GSK, Merck, Abbvie, Sanofi, Medicago, BioNtech, Moderna, BMS, Novavax, SK Biosciences, Gilead, and Sanaria.
Databáze:	MEDLINE
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