Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 From Approved Monoclonal Antibodies
Article Sidebar
Main Article Content
Abstract
Background: 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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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: 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: 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 KP.3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP.3.3.
Conclusions: Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Pathogens and Immunity abides by Creative Commons BY 4.0:
http://creativecommons.org/licenses/by/4.0/
This license lets others distribute, remix, tweak, and build upon your work for any lawful purpose, even commercially, as long as they credit you for the original creation. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials. The authors maintain copyright of their materal.
*Due to a template error on our pdfs, articles published from May 20, 2016 to June 24, 2022 incorrectly state the copyright is held by Pathogens and Immunity. Copyright of all articles is held by the authors of each article as noted in the above copyright policy.
References
1. Planas D, Staropoli I, Michel V, Lemoine F, Donati F, Prot M, Porrot F, Guivel-Benhassine F, Jeyarajah B, Brisebarre A, Dehan O, Avon L, Bolland WH, Hubert M, Buchrieser J, Vanhoucke T, Rosenbaum P, Veyer D, Pere H, Lina B, Trouillet-Assant S, Hocqueloux L, Prazuck T, Simon-Loriere E, Schwartz O. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion. Nat Commun. 2024;15(1):2254. doi: 10.1038/s41467-024-46490-7. PubMed PMID: 38480689; PMCID: PMC10938001.
2. Kaku Y, Yo MS, Tolentino JE, Uriu K, Okumura K, Genotype to Phenotype Japan C, Ito J, Sato K. Virological characteristics of the SARS-CoV-2 KP.3, LB.1, and KP.2.3 variants. Lancet Infect Dis. 2024;24(8):e482-e3. doi: 10.1016/S1473-3099(24)00415-8. PubMed PMID: 38945150.
3. Kaku Y, Uriu K, Kosugi Y, Okumura K, Yamasoba D, Uwamino Y, Kuramochi J, Sadamasu K, Yoshimura K, Asakura H, Nagashima M, Genotype to Phenotype Japan C, Ito J, Sato K. Virological characteristics of the SARS-CoV-2 KP.2 variant. Lancet Infect Dis. 2024;24(7):e416. doi: 10.1016/S1473-3099(24)00298-6. PubMed PMID: 38782005.
4. Focosi D, Franchini M, Casadevall A, Maggi F. An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2. Clin Microbiol Infect. 2024;30(8):999-1006. doi: 10.1016/j.cmi.2024.04.012. PubMed PMID: 38663655.
5. Cai Y, Diallo S, Rosenthal K, Ren K, Flores DJ, Dippel A, Oganesyan V, van Dyk N, Chen X, Cantu E, Choudhary R, Sulikowski M, Adissu H, Chawla B, Kar S, Liu C, Dijokaite-Guraliuc A, Mongkolsapaya J, Rajan S, Loo YM, Beavon R, Webber C, Chang LJ, Thomas S, Clegg L, Zhang H, Screaton GR, Philbin N, Harre M, Selim A, Martinez-Alier N, Uriel A, Cohen TS, Perez JL, Esser MT, Blair W, Francica JR. AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults. Sci Transl Med. 2024;16(753):eado2817. doi: 10.1126/scitranslmed.ado2817. PubMed PMID: 38924429.
6. AstraZeneca. Sipavibart EMA regulatory submission accepted under accelerated assessment for COVID-19 prevention. 2024.
7. Fact sheet for healthcare providers: Emergency Use Authorization of Pemgarda (pemivibart). Invivyd; 2024. Accessed March 25, 2024. In: Pemgarda, editor.: FDA.gov; 2024.
8. Cao Y, Jian F, Zhang Z, Yisimayi A, Hao X, Bao L, Yuan F, Yu Y, Du S, Wang J, Xiao T, Song W, Zhang Y, Liu P, An R, Wang P, Wang Y, Yang S, Niu X, Zhang Y, Gu Q, Shao F, Hu Y, Yin W, Zheng A, Wang Y, Qin C, Jin R, Xiao J, Xie XS. Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents. Cell Rep. 2022;41(12):111845. doi: 10.1016/j.celrep.2022.111845. PubMed PMID: 36493787; PMCID: PMC9712074.
9. Yang S, Yu Y, Xu Y, Jian F, Song W, Yisimayi A, Wang P, Wang J, Liu J, Yu L, Niu X, Wang J, Wang Y, Shao F, Jin R, Wang Y, Cao Y. Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure. Lancet Infect Dis. 2024;24(2):e70-e2. doi: 10.1016/S1473-3099(23)00744-2. PubMed PMID: 38109919.
10. Beijing Boren Hospital. Efficacy and Safety of the Anti-COVID-19 Antibody SA55 for Injection in Patients With Hematological Disorders Who Are Persistently Positive for COVID-19 [Internet]. ClinicalTrials.gov identifier: NCT123456. Available from: https://clinicaltrials.gov/study/NCT05675943.
11. Buchrieser J, Dufloo J, Hubert M, Monel B, Planas D, Rajah MM, Planchais C, Porrot F, Guivel-Benhassine F, Van der Werf S, Casartelli N, Mouquet H, Bruel T, Schwartz O. Syncytia formation by SARS-CoV-2-infected cells. EMBO J. 2020;39(23):e106267. doi: 10.15252/embj.2020106267. PubMed PMID: 33051876; PMCID: PMC7646020.
12. Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, Bolland WH, Porrot F, Staropoli I, Lemoine F, Pere H, Veyer D, Puech J, Rodary J, Baele G, Dellicour S, Raymenants J, Gorissen S, Geenen C, Vanmechelen B, Wawina-Bokalanga T, Marti-Carreras J, Cuypers L, Seve A, Hocqueloux L, Prazuck T, Rey FA, Simon-Loriere E, Bruel T, Mouquet H, Andre E, Schwartz O. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature. 2022;602(7898):671-5. doi: 10.1038/s41586-021-04389-z. PubMed PMID: 35016199.
13. Planas D, Bruel T, Grzelak L, Guivel-Benhassine F, Staropoli I, Porrot F, Planchais C, Buchrieser J, Rajah MM, Bishop E, Albert M, Donati F, Prot M, Behillil S, Enouf V, Maquart M, Smati-Lafarge M, Varon E, Schortgen F, Yahyaoui L, Gonzalez M, De Seze J, Pere H, Veyer D, Seve A, Simon-Loriere E, Fafi-Kremer S, Stefic K, Mouquet H, Hocqueloux L, van der Werf S, Prazuck T, Schwartz O. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021;27(5):917-24. doi: 10.1038/s41591-021-01318-5. PubMed PMID: 33772244.
14. Bruel T, Hadjadj J, Maes P, Planas D, Seve A, Staropoli I, Guivel-Benhassine F, Porrot F, Bolland WH, Nguyen Y, Casadevall M, Charre C, Pere H, Veyer D, Prot M, Baidaliuk A, Cuypers L, Planchais C, Mouquet H, Baele G, Mouthon L, Hocqueloux L, Simon-Loriere E, Andre E, Terrier B, Prazuck T, Schwartz O. Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies. Nat Med. 2022;28(6):1297-302. doi: 10.1038/s41591-022-01792-5. PubMed PMID: 35322239; PMCID: 35322239.
15. Planchais C, Fernandez I, Bruel T, de Melo GD, Prot M, Beretta M, Guardado-Calvo P, Dufloo J, Molinos-Albert LM, Backovic M, Chiaravalli J, Giraud E, Vesin B, Conquet L, Grzelak L, Planas D, Staropoli I, Guivel-Benhassine F, Hieu T, Boulle M, Cervantes-Gonzalez M, Ungeheuer MN, Charneau P, van der Werf S, Agou F, French CCSG, Group CS, Dimitrov JD, Simon-Loriere E, Bourhy H, Montagutelli X, Rey FA, Schwartz O, Mouquet H. Potent human broadly SARS-CoV-2-neutralizing IgA and IgG antibodies effective against Omicron BA.1 and BA.2. J Exp Med. 2022;219(7). doi: 10.1084/jem.20220638. PubMed PMID: 35704748; PMCID: PMC9206116.
16. Elbe S, Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health. Glob Chall. 2017;1(1):33-46. doi: 10.1002/gch2.1018. PubMed PMID: 31565258; PMCID: PMC6607375.
17. Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 2017;22(13):30494. doi: 10.2807/1560-7917.ES.2017.22.13.30494. PubMed PMID: 28382917; PMCID: PMC5388101.
18. Tsueng G, Mullen JL, Alkuzweny M, Cano M, Rush B, Haag E, Lin J, Welzel DJ, Zhou X, Qian Z, Latif AA, Hufbauer E, Zeller M, Andersen KG, Wu C, Su AI, Gangavarapu K, Hughes LD. Outbreak.info Research Library: a standardized, searchable platform to discover and explore COVID-19 resources. Nat Methods. 2023;20(4):536-40. doi: 10.1038/s41592-023-01770-w. PubMed PMID: 36823331; PMCID: PMC10393269.
19. Wang Q, Guo Y, Ho J, Ho DD. Pemivibart is less active against recent SARS-CoV-2 JN.1 sublineages. bioRxiv. 2024:2024.08.12.607496. doi: 10.1101/2024.08.12.607496.