Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract Therapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce conserved receptor-binding domain (RBD) regions for protection variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges viruses whose were matched or mismatched to those nanoparticles. Here, describe neutralizing mAbs mosaic-8b–immunized rabbits, some par with Pemgarda (the only currently FDA-approved therapeutic mAb). Deep mutational scanning, in vitro selection resistance mutations, cryo-EM structures spike-antibody complexes demonstrated targeting epitopes. Rabbit included critical D-gene segment features common human anti-RBD mAbs, despite rabbit genomes lacking an equivalent segment. Thus, mosaic RBD-nanoparticle immunization coupled multiplexed screening represent efficient way generate select pan-sarbecovirus pan-SARS-2 variant mAbs.

Language: Английский

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SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

The immune response to viral infection is shaped by past exposures related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted spike from an early strain, either through vaccination or during stages COVID-19 pandemic. As consequence this imprinting, with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited imprinting strain. Here we compare neutralizing antibody specificities individuals versus infants infected Specifically, use pseudovirus-based deep mutational scanning measure how mutations affect neutralization serum adults and children original vaccine primary XBB* variant. While activity targets receptor-binding domain (RBD), only mostly N-terminal (NTD). In these infants, secondary exposure via shifts towards RBD, although specific RBD sites targeted are different than for adults. dramatic differences in among histories likely impact evolution.

Language: Английский

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SA55 broadly neutralizes SARS-CoV-2 and robustly prevents viral escape by JN.1 sublineages

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

SARS-CoV-2 monoclonal antibodies remain the only option for prevention or treatment of COVID-19 those with immunodeficiencies drug interactions antiviral agents. Here, we assess neutralizing activity authorized antibody pemivibart and candidate SA55 against major historical currently dominant viral variants, including JN.1 subvariants KP.3.1.1 XEC. Our findings show that demonstrates broad potency while exhibits reduced variants. Then employ replication-competent vesicular stomatitis virus spike (rVSVΔG-JN.1) to select escape variants SA55. Following this, conduct a systematic comparison profiles these two antibodies, revealing is remarkably resilient mutations under selection, which consistent our SPR data indicating possesses substantially stronger binding affinity. Moreover, an immunobridging analysis suggests may have superior clinical efficacy in preventing infection current variant landscape. Together, this work highlights promise as potential therapeutic COVID-19, especially immunocompromised populations.

Language: Английский

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Sipavibart: when a success changes into a failure

The Lancet Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Development of antiviral drugs for COVID-19 in 2025: unmet needs and future challenges

Expert Review of Anti-infective Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The success in the COVID-19 pandemic containment largely originated from vaccine- and infection-elicited immunity, with SARS-CoV-2 infection only marginally mitigated by availability of antiviral drugs. current lack effective prophylactic therapeutic agents immunocompromised patients highlights need for a radical change design both drug manufacturing clinical trials. In this review authors summarize their suggestions manufacturers, reviewing classes small molecule antivirals passive immunotherapies highlighting limitations unexploited potential. Molecular serological testing can improve appropriateness. Efficacy be improved combining different while preserving economical sustainability. Respiratory delivery should better investigated

Language: Английский

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Potent bivalent nanobody constructs that protect against the SARS-CoV-2 XBB variant

npj Viruses, Journal Year: 2025, Volume and Issue: 3(1)

Published: March 13, 2025

Language: Английский

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SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals

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

Published: March 25, 2025

ABSTRACT The immune response to viral infection is shaped by past exposures related virus strains, a phenomenon known as imprinting. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), much of the population has been imprinted spike from an early strain, either through vaccination or during stages COVID-19 pandemic. As consequence this imprinting, with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited imprinting strain. Here we compare neutralizing antibody specificities individuals versus infants infected Specifically, use pseudovirus-based deep mutational scanning measure how mutations affect neutralization serum adults and children original vaccine primary XBB* variant. While activity targets receptor-binding domain (RBD), only mostly N-terminal domain. In these infants, secondary exposure via shifts toward RBD, although specific RBD sites targeted are different adults. dramatic differences in among histories likely impact evolution. IMPORTANCE We show that person’s history strongly affects which regions on their target. particular, who have just once strain make target than exposed both older strains. This person-to-person heterogeneity means same mutation can impacts immunity people.

Language: Английский

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Management of SARS-CoV-2 Infection-Clinical Practice Guidelines of the Polish Association of Epidemiologists and Infectiologists, for 2025

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2305 - 2305

Published: March 27, 2025

The first Polish recommendations for the management of COVID-19 were published by Society Epidemiologists and Infectiologists (PTEiLChZ) on 31 March 2020, last three years ago. emergence new SARS-CoV-2 variants, a different course disease, as well knowledge about therapies vaccines, requires updating diagnostic, therapeutic, prophylactic guidelines. Despite reduction in threat associated with COVID-19, there is risk another epidemic caused coronaviruses, which was an additional reason developing version In preparing these recommendations, Delphi method used, reaching consensus after survey cycles. Compared to 2022 version, names individual stages disease have been changed, adapting them realities clinical practice, attention paid differences observed immunosuppressed patients children. Some previously recommended drugs discontinued, including monoclonal antibodies. addition, general principles vaccination presented, issues related post-COVID syndrome.

Language: Английский

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Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115543 - 115543

Published: April 1, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread, it remains critical understand the functional consequences of mutations in dominant viral variants. The recombinant JN.1 subvariant XEC recently replaced KP.3.1.1 become most prevalent worldwide. Here, we measure vitro neutralization by human sera, monoclonal antibodies, soluble ACE2 (hACE2) receptor relative parental subvariants KP.3 JN.1. are slightly more resistant (1.3- 1.6-fold) than serum antigenically similar. Both also demonstrate greater resistance select antibodies hACE2, all which target top spike. Our findings suggest that upward motion receptor-binding domain spike may be partially hindered N-terminal XEC, allowing these better evade up position have a growth advantage.

Language: Английский

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Structural and Functional Insights into the Evolution of SARS-CoV-2 KP.3.1.1 Spike Protein

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

Published: Dec. 10, 2024

Summary The JN.1-sublineage KP.3.1.1 recently emerged as the globally prevalent SARS-CoV-2 variant, demonstrating increased infectivity and antibody escape. We investigated how mutations a deletion in spike protein (S) affect ACE2 binding Mass spectrometry revealed new glycan site at residue N30 altered glycoforms neighboring N61. Cryo-EM structures showed that rearrangement of adjacent residues did not significantly change overall structure, up-down ratio receptor-binding domains (RBDs), or binding. Furthermore, S structure with hACE2 further confirmed an epistatic effect between F456L Q493E on Our analysis shows variants after late 2023 are now incorporating reversions to found other sarbecoviruses, including glycan, Q493E, others. Overall, these results inform structural functional consequences mutations, current evolutionary trajectory, immune evasion.

Language: Английский

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