Pre-exposure antibody prophylaxis protects macaques from severe influenza

Science, Journal Year: 2025, Volume and Issue: 387(6733), P. 534 - 541

Published: Jan. 30, 2025

Influenza virus pandemics and seasonal epidemics have claimed countless lives. Recurrent zoonotic spillovers of influenza viruses with pandemic potential underscore the need for effective countermeasures. In this study, we show that pre-exposure prophylaxis broadly neutralizing antibody (bnAb) MEDI8852 is highly in protecting cynomolgus macaques from severe disease caused by aerosolized pathogenic avian H5N1 infection. Protection was dose–dependent yet independent Fc-mediated effector functions at dose tested. Macaques receiving 10 milligrams per kilogram or higher had negligible impairment respiratory function after infection, whereas control animals were not protected fatality. Given breadth other bnAbs, anticipate protection unforeseen A achievable.

Language: Английский

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Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase

Immunity, Journal Year: 2023, Volume and Issue: 56(11), P. 2621 - 2634.e6

Published: Nov. 1, 2023

Language: Английский

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Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase

Immunity, Journal Year: 2024, Volume and Issue: 57(3), P. 574 - 586.e7

Published: March 1, 2024

Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug vaccine target, our understanding of the NA antigenic landscape still remains incomplete. Here, we describe NA-specific human antibodies that target underside globular head domain, inhibit propagation a wide range H3N2, swine-origin variant H2N2 viruses, confer both pre- post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures two such complex with reveal non-overlapping epitopes covering head. These sites are highly conserved among N2 NAs yet inaccessible unless tilts or dissociates. Our findings help guide development countermeasures ever-changing by identifying hidden vulnerability on underside.

Language: Английский

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Anti-neuraminidase immunity in the combat against influenza

Expert Review of Vaccines, Journal Year: 2024, Volume and Issue: 23(1), P. 474 - 484

Published: April 18, 2024

Anti-neuraminidase (NA) immunity correlates with the protection against influenza virus infection in both human and animal models. The aim of this review is to better understand mechanism anti-NA immunity, also evaluate approaches on developing NA-based vaccines or enhancing immune responses NA for current vaccines.

Language: Английский

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A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing sufficiently potent clinical development and retain activity despite remain elusive. We identified human mAb, designated VIR-7229, which targets the receptor-binding motif (RBM) with unprecedented cross-reactivity all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently SARS-CoV-2 variants since 2019, recent EG.5, BA.2.86, JN.1. VIR-7229 tolerates extraordinary variability, partly attributed its high binding affinity, receptor molecular mimicry, interactions RBM backbone atoms. Consequently, features barrier selection of mutants, rare associated reduced fitness, underscoring potential be future evolution. is strong candidate become next-generation medicine.

Language: Английский

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Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Feb. 13, 2025

Language: Английский

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Intranasal administration of a panreactive influenza antibody reveals Fc-independent mode of protection

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 8, 2025

Language: Английский

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Influenza B virus neuraminidase: a potential target for next-generation vaccines?

Expert Review of Vaccines, Journal Year: 2023, Volume and Issue: 23(1), P. 39 - 48

Published: Dec. 1, 2023

Influenza B viruses (IBV) cause a significant health and economic burden annually. Due to lower antigenic drift rate, less extensive diversity, lack of animal reservoirs, the development highly effective universal vaccines against IBV might be in reach. Current seasonal influenza are formulated induce antibodies Hemagglutinin (HA) protein, but their effectiveness is reduced by mismatch between vaccine circulating strains.

Language: Английский

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Targeting neuraminidase: the next frontier for broadly protective influenza vaccines

Trends in Immunology, Journal Year: 2023, Volume and Issue: 45(1), P. 11 - 19

Published: Dec. 15, 2023

Language: Английский

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Broadly neutralizing antibodies to combat influenza virus infection

Antiviral Research, Journal Year: 2023, Volume and Issue: 221, P. 105785 - 105785

Published: Dec. 23, 2023

Language: Английский

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