Structure and function of an unusual R452-dependent monoclonal antibody against SARS-CoV-2

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) variants is still a major public health concern worldwide. Currently, SARS-CoV-2 have been widely used to develop the updated vaccine. However, whether these mutated residues good immunogenicity remains elusive. In particular, we know little about what kind of antibodies can be induced infection or vaccination and their biological characteristics. Here, identified an R452-dependent monoclonal neutralizing antibody, ConD-852, from primarily Delta variant-infected individual, indicating that R452 residue has immunogenicity. We determined high-resolution cryo-electron microscopy (cryo-EM) structure ConD-852 complexed with receptor-binding domain (RBD), revealing how it binds R452-related epitopes detailed interactions. Interestingly, could only bind amino acid “R” at 452 position on RBD, displaying strict restriction recognize SARS-CoV-2. Overall, our findings regarding confirmed carrying L452R mutation enriched knowledge binding model involving antibody virus. IMPORTANCE Although update COVID-19 vaccine candidate, mutations unknown. This study demonstrates induce potent reports cryo-EM around RBD.

Language: Английский

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Public antibodies: convergent signatures in human humoral immunity against pathogens

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

ABSTRACT The human humoral immune system has evolved to recognize a vast array of pathogenic threats. This ability is primarily driven by the immense diversity antibodies generated gene rearrangement during B cell development. However, different people often produce strikingly similar when exposed same antigen—known as public antibodies. Public not only reflect system’s consistently select for optimal cells but can also serve signatures responses triggered infection and vaccination. In this Minireview, we examine compare antibody identification methods, including criteria used based on V(D)J usage similarity in complementarity-determining region three sequences, explore molecular features elicited against common pathogens, viruses, protozoa, bacteria. Finally, discuss evolutionary significance potential applications informing design germline-targeting vaccines, predicting escape mutations emerging providing insights into process affinity maturation. ongoing discovery response pathogens holds improve pandemic preparedness, accelerate vaccine efforts, deepen our understanding biology.

Language: Английский

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Longitudinal profiling of B cells primed by mRNA vaccine and recalled by Omicron variants uncovers antibodies broadly neutralizing sarbecoviruses

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Regarding to the impact of ancestral SARS-CoV-2 immune imprinting on antibody responses emerging variants, what extent memory B cells elicited by wild-type (WT) spike can develop neutralizing breadth and potency in recalls is a key question. Here, we longitudinally tracked recognizing WT two individuals mRNA vaccine, from convalescence breakthrough infection acute phase reinfection. Comprehensive characterization 632 monoclonal antibodies (mAbs) those reveals that mAbs cloned after reinfection have dramatically enhanced potency, including 11 potently neutralize all tested variants KP.3. Among mAbs, 5 are classified into public clonotypes encoded IGHV3-53 or IGHV3-66, whereas rest belong rare clonotype IGHV3-74. Notably, IGHV3-74 even SARS-CoV-1 with minimum IC50 0.055 μg/ml. Structural functional analysis further suggests target novel epitope receptor-binding domain, best mAb, termed KXD352, highly resilient variations this epitope. Overall, study demonstrates both primed prototype vaccine achieve extraordinary repeated Omicron infections.

Language: Английский

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Development of a two-component recombinant vaccine for COVID-19

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 20, 2024

Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues pose significant threat human society. Vaccination remains one most effective methods for preventing COVID-19. While antigenic regions are found in receptor binding domain (RBD), N-terminal (NTD) S protein is another crucial region inducing neutralizing antibodies (nAbs) against

Language: Английский

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