Antibody feedback regulates immune memory after SARS-CoV-2 mRNA vaccination

Nature, Journal Year: 2022, Volume and Issue: 613(7945), P. 735 - 742

Published: Dec. 6, 2022

Abstract Feedback inhibition of humoral immunity by antibodies was first documented in 1909 1 . Subsequent studies showed that, depending on the context, can enhance or inhibit immune responses 2,3 However, little is known about how pre-existing influence development memory B cells. Here we examined cell response individuals who received two high-affinity anti-SARS-CoV-2 monoclonal and subsequently doses an mRNA vaccine 4–8 We found that recipients produced antigen-binding neutralizing titres were only fractionally lower compared than control individuals. cells differed from those they predominantly expressed low-affinity IgM carried small numbers somatic mutations altered receptor binding domain (RBD) target specificity, consistent with epitope masking. Moreover, out 77 anti-RBD tested neutralized virus. The mechanism underlying these findings experiments mice germinal centres formed presence same dominated Our results indicate bias centre selection through distinct mechanisms: (1) lowering activation threshold for cells, thereby permitting abundant lower-affinity clones to participate response; (2) direct masking their cognate epitopes. This may part explain shifting profile elicited booster vaccinations 9

Language: Английский

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

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(4), P. 569 - 580

Published: April 3, 2023

Language: Английский

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Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1711 - 1724

Published: Sept. 21, 2023

Language: Английский

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Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 19, 2023

Waves of SARS-CoV-2 infection have resulted from the emergence viral variants with neutralizing antibody resistance mutations. Simultaneously, repeated antigen exposure has generated affinity matured B cells, producing broadly receptor binding domain (RBD)-specific antibodies activity against emergent variants. To determine how might escape these antibodies, we subjected chimeric viruses encoding spike proteins ancestral, BA.1 or BA.2 to selection by 40 antibodies. We identify numerous examples epistasis, whereby in vitro selected and naturally occurring substitutions RBD epitopes that do not confer Wuhan-Hu-1 spike, so spikes. As few as 2 3 BA.5 nearly all substantial plasma most individuals. Thus, epistasis facilitates acquisition remained effective early omicron

Language: Английский

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Evolution of antibody immunity following Omicron BA.1 breakthrough infection

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 12, 2023

Understanding the longitudinal dynamics of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform development next-generation vaccines. Here, we track SARS-CoV-2 receptor binding domain (RBD)-specific responses up to six months Omicron BA.1 in mRNA-vaccinated individuals. Cross-reactive serum neutralizing and memory B cell (MBC) decline by two- four-fold through study period. Breakthrough elicits minimal de novo BA.1-specific but drives affinity maturation pre-existing cross-reactive MBCs toward BA.1, which translates into enhanced breadth activity across other variants. Public clones dominate response at both early late time points breakthough infection, their escape mutation profiles predict newly emergent sublineages, suggesting that convergent continue shape evolution. While is limited our relatively small cohort size, these results suggest variant exposure evolution memory, supporting continued variant-based

Language: Английский

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Immune imprinting and next-generation coronavirus vaccines

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(11), P. 1971 - 1985

Published: Nov. 6, 2023

Language: Английский

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Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 912 - 925.e4

Published: March 14, 2024

Language: Английский

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Immune Imprinting and Implications for COVID-19

Vaccines, Journal Year: 2023, Volume and Issue: 11(4), P. 875 - 875

Published: April 20, 2023

Immunological memory is the key source of protective immunity against pathogens. At current stage COVID-19 pandemic, heterologous combinations exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, downside memory, might limit generation de novo immune response variant or next-generation vaccines. Here, we review mechanistic basis imprinting by focusing on B cell immunobiology and discuss extent which harmful, as well its effect SARS-CoV-2 vaccination.

Language: Английский

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AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans

Science Immunology, Journal Year: 2024, Volume and Issue: 9(94)

Published: April 5, 2024

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to generation antigen-specific B cell clones with distinct specificities or maturation memory that produce broadly cross-reactive antibodies unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted AS03 (CoVLP+AS03), messenger RNA (mRNA-1273). CoVLP+AS03 enhanced magnitude and durability circulating CD4 + T responses. Antigen-specific cells group at day 42 correlated 6 months. induced which accumulated somatic hypermutations over months, resulting neutralization monoclonal antibodies. Furthermore, fraction neutralizing encoded by increased between These results indicate enhances antigenic clonal level induces progressive response.

Language: Английский

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SARS-CoV-2 Omicron BA.1 breakthrough infection drives late remodeling of the memory B cell repertoire in vaccinated individuals

Immunity, Journal Year: 2023, Volume and Issue: 56(9), P. 2137 - 2151.e7

Published: Aug. 4, 2023

Language: Английский

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