Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(23)

Опубликована: Окт. 11, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and also only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine then transferred sera from these into naive mice, followed by challenge show that received or mAb exhibited enhanced control of Nucleocapsid-specific elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) infected cells. To our knowledge, findings provide demonstration literature specific nucleocapsid clearance, providing rationale clinical evaluation therapies treat COVID-19.

Язык: Английский

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Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 21, 2022

T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence this is lacking. Here, we associated whole-blood-based measurement SARS-CoV-2-specific interferon-γ-positive cell responses with positive COVID-19 diagnostic (PCR and/or lateral flow) test results up 6 months post-blood sampling. Amongst 148 participants donating venous blood samples, response magnitude significantly greater in those who remain protected versus become infected (P < 0.0001); relatively low a 43.2% risk infection, whereas high reduces 5.4%. These findings recapitulated further 299 testing scalable capillary blood-based assay that could facilitate the acquisition population-scale immunity data (14.9% 4.4%, respectively). Hence, can prognosticate should be assessed when monitoring individual population status.

Язык: Английский

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In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms

Cellular and Molecular Immunology, Год журнала: 2023, Номер 21(2), С. 103 - 118

Опубликована: Дек. 26, 2023

Abstract Members of the coronaviridae family are endemic to human populations and have caused several epidemics pandemics in recent history. In this review, we will discuss feasibility progress toward ultimate goal creating a pan-coronavirus vaccine that can protect against infection disease by all members coronavirus family. We detail unmet clinical need associated with continued transmission SARS-CoV-2, MERS-CoV four seasonal coronaviruses (HCoV-OC43, NL63, HKU1 229E) humans potential for future zoonotic coronaviruses. highlight how first-generation SARS-CoV-2 vaccines natural history studies greatly increased our understanding effective antiviral immunity informed next-generation design. then consider ideal properties propose blueprint type may offer cross-protection. Finally, describe subset diverse technologies novel approaches being pursued developing broadly or universally protective

Язык: Английский

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Pre-existing immunity modulates responses to mRNA boosters

Cell Reports, Год журнала: 2023, Номер 42(3), С. 112167 - 112167

Опубликована: Фев. 15, 2023

mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although boosters being implemented, extent to which pre-existing influences efficacy remains unclear. In a cohort individuals primed with mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost associated higher fold-increase after boost, suggesting modulates immunogenicity vaccines. Our studies mice show antibodies accelerate clearance vaccine antigen via Fc-dependent mechanisms, limiting amount available prime B cell responses These data demonstrate "tug war" between de novo following vaccination, they suggest transient downmodulation effector function may improve

Язык: Английский

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Defining the role of natural killer cells in COVID-19

Nature Immunology, Год журнала: 2023, Номер 24(10), С. 1628 - 1638

Опубликована: Июль 17, 2023

Язык: Английский

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Systems analysis of innate and adaptive immunity in Long COVID

Seminars in Immunology, Год журнала: 2024, Номер 72, С. 101873 - 101873

Опубликована: Март 1, 2024

Язык: Английский

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Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 3, 2024

Abstract The repeat emergence of SARS-CoV-2 variants concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need develop next-generation vaccine candidates that confer broad protection. Here we describe antibody response induced by Spike Ferritin Nanoparticle (SpFN) candidate adjuvanted Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal directed against Receptor Binding Domain (RBD), N-Terminal (NTD), or S2 Domain, define molecular recognition cross-reactive (mAbs) elicited SpFN. We identify six neutralizing sarbecovirus cross-reactivity recapitulate serum polyclonal responses. In particular, RBD mAb WRAIR-5001 binds conserved cryptic region high affinity clades 1 2, Omicron variants, while WRAIR-5021 offers complete protection from B.1.617.2 (Delta) a murine challenge study. Our data further highlight ability SpFN vaccination stimulate B cells targeting regions activity SARS CoV-1 variants.

Язык: Английский

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SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D

Cell Reports, Год журнала: 2022, Номер 41(13), С. 111892 - 111892

Опубликована: Дек. 1, 2022

Язык: Английский

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Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5352 - 5352

Опубликована: Март 10, 2023

More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused unforeseen COVID-19 pandemic with millions of deaths. In meantime, SARS-CoV-2 has become endemic and is now part repertoire viruses causing seasonal severe respiratory infections. Due to several factors, among them development immunity through natural infection, vaccination current dominance seemingly less pathogenic strains belonging omicron lineage, situation stabilized. However, challenges remain possible new occurrence highly variants remains a threat. Here we review development, features importance assays measuring neutralizing antibodies (NAbs). particular focus on in vitro infection molecular interaction studying binding receptor domain (RBD) its cognate cellular ACE2. These assays, but not measurement SARS-CoV-2-specific per se, can inform us whether produced by convalescent or vaccinated subjects may protect against thus have potential predict risk becoming newly infected. This information extremely important given fact that considerable number subjects, vulnerable persons, respond poorly production antibodies. Furthermore, these allow determine evaluate virus-neutralizing capacity induced vaccines administration plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 synthetic compounds be used for therapy assist preclinical evaluation vaccines. Both types relatively quickly adapted emerging virus about magnitude cross-neutralization, which even estimate infected appearing variants. Given paramount discuss their specific features, advantages disadvantages, technical aspects yet fully resolved issues, such as cut-off levels predicting degree vivo protection.

Язык: Английский

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Identification of soluble biomarkers that associate with distinct manifestations of long COVID

Nature Immunology, Год журнала: 2025, Номер 26(5), С. 692 - 705

Опубликована: Апрель 30, 2025

Язык: Английский

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