Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies.
Pemivibart
SARS-CoV-2 variants
Sipavibart
monoclonal antibodies
neutralization
Journal
Pathogens & immunity
ISSN: 2469-2964
Titre abrégé: Pathog Immun
Pays: United States
ID NLM: 101683909
Informations de publication
Date de publication:
2024
2024
Historique:
received:
20
08
2024
accepted:
04
09
2024
medline:
11
10
2024
pubmed:
11
10
2024
entrez:
11
10
2024
Statut:
epublish
Résumé
First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants. In 2024, 2 novel mAbs, VYD222/Pemivibart and AZD3152/Sipavibart, were approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. We isolated authentic JN.1.1, KP.1.1, LB.1, and KP.3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in 2 target cell lines. Compared to ancestral strains, VYD222/Pemivibart remained moderately active against JN.1 subvariants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 µg/mL for KP3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP3.3. Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.
Sections du résumé
Background
UNASSIGNED
First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants. In 2024, 2 novel mAbs, VYD222/Pemivibart and AZD3152/Sipavibart, were approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized.
Methods
UNASSIGNED
We isolated authentic JN.1.1, KP.1.1, LB.1, and KP.3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in 2 target cell lines.
Results
UNASSIGNED
Compared to ancestral strains, VYD222/Pemivibart remained moderately active against JN.1 subvariants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 µg/mL for KP3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP3.3.
Conclusions
UNASSIGNED
Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.
Identifiants
pubmed: 39391808
doi: 10.20411/pai.v10i1.752
pii: pai.v10i1.752
pmc: PMC11464000
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1-11Informations de copyright
Copyright © 2024 Pathogens and Immunity.
Déclaration de conflit d'intérêts
CP, HM, and OS have a patent application for anti-SARS-CoV-2 monoclonal antibodies not used in the present study (PCT/FR2021/070522, WO 2022/228827A1), and HM is a scientific consultant for SpikImm biotech. The remaining authors declare no competing interests.