Human Monoclonal Antibody F61 Nasal Spray Effectively Protected High-risk Populations from SARS-CoV-2 Variants During the COVID-19 Pandemic from Late 2022 to Early 2023 in China

Overview

Journal Emerg Microbes Infect

Specialty Infectious Diseases

Date 2023 Nov 16

PMID 37970736

Authors

Ying Liu

Jiayou Zhang

Wen Liu

Yongbing Pan

Shunan Ruan

Xuanxuan Nian

Wei Chen

Lina Sun

Qiangling Yin

Xin Yue

Qingliang Li

Fang Gui

Cong Wu

Shuzhen Wang

Yunkai Yang

Zhaofei Jing

Feiguang Long

Zejun Wang

Zeyu Zhang

Chaolin Huang

Kai Duan

Mifang Liang

Xiaoming Yang

Affiliations

Soon will be listed here.

Abstract

Following the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (-3.74%-10.75%) in the one-dose cohort and 72.19% (57.33%-81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.

References

Prince G, Hemming V, Horswood R, Baron P, Chanock R . Effectiveness of topically administered neutralizing antibodies in experimental immunotherapy of respiratory syncytial virus infection in cotton rats. J Virol. 1987; 61(6):1851-4. PMC: 254189. DOI: 10.1128/JVI.61.6.1851-1854.1987. View

Totschnig D, Augustin M, Niculescu I, Laferl H, Jansen-Skoupy S, Lehmann C . SARS-CoV-2 Pre-Exposure Prophylaxis with Sotrovimab and Tixagevimab/Cilgavimab in Immunocompromised Patients-A Single-Center Experience. Viruses. 2022; 14(10). PMC: 9607212. DOI: 10.3390/v14102278. View

Zhang Z, Li H, Ma H, Wang W, Gao D, Ye F . Genomic Recombination of SARS-CoV-2 Subvariants BA.5.2.48 and BF.7.14 - China, 2023. China CDC Wkly. 2023; 5(14):318-320. PMC: 10182904. DOI: 10.46234/ccdcw2023.058. View

Yang M, Li J, Huang Z, Li H, Wang Y, Wang X . Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain. Microbiol Spectr. 2021; 9(2):e0135221. PMC: 8515945. DOI: 10.1128/Spectrum.01352-21. View

Song R, Zeng G, Yu J, Meng X, Chen X, Li J . Post-exposure prophylaxis with SA58 (anti-SARS-COV-2 monoclonal antibody) nasal spray for the prevention of symptomatic COVID-19 in healthy adult workers: a randomized, single-blind, placebo-controlled clinical study. Emerg Microbes Infect. 2023; 12(1):2212806. PMC: 10215016. DOI: 10.1080/22221751.2023.2212806. View

Lu J, Yin Q, Pei R, Zhang Q, Qu Y, Pan Y . Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants. Virol Sin. 2022; 37(2):238-247. PMC: 8855614. DOI: 10.1016/j.virs.2022.02.005. View

Qu Y, Zhang X, Wang M, Sun L, Jiang Y, Li C . Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants. Virol Sin. 2021; 36(5):934-947. PMC: 8255729. DOI: 10.1007/s12250-021-00409-4. View

Cucinotta D, Vanelli M . WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 91(1):157-160. PMC: 7569573. DOI: 10.23750/abm.v91i1.9397. View

Balmforth D, Swales J, Silpa L, Dunton A, Davies K, Davies S . Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial. J Clin Virol. 2022; 155:105248. PMC: 9313533. DOI: 10.1016/j.jcv.2022.105248. View

10.

Matucci A, Vultaggio A, Danesi R . The use of intravenous versus subcutaneous monoclonal antibodies in the treatment of severe asthma: a review. Respir Res. 2018; 19(1):154. PMC: 6097430. DOI: 10.1186/s12931-018-0859-z. View

11.

Lu G, Ling Y, Jiang M, Tan Y, Wei D, Jiang L . Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland. Front Med. 2023; 17(4):758-767. PMC: 10064619. DOI: 10.1007/s11684-022-0981-7. View

12.

Ku Z, Xie X, Hinton P, Liu X, Ye X, Muruato A . Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Nature. 2021; 595(7869):718-723. PMC: 8742224. DOI: 10.1038/s41586-021-03673-2. View

13.

Weltzin R, Traina-Dorge V, Soike K, Zhang J, Mack P, Soman G . Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection. J Infect Dis. 1996; 174(2):256-61. DOI: 10.1093/infdis/174.2.256. View

14.

Leyva-Grado V, Tan G, Leon P, Yondola M, Palese P . Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza virus monoclonal antibodies. Antimicrob Agents Chemother. 2015; 59(7):4162-72. PMC: 4468714. DOI: 10.1128/AAC.00290-15. View

15.

Li X, Pan Y, Yin Q, Wang Z, Shan S, Zhang L . Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages. Cell Discov. 2022; 8(1):87. PMC: 9453709. DOI: 10.1038/s41421-022-00449-4. View

16.

De Gasparo R, Pedotti M, Simonelli L, Nickl P, Muecksch F, Cassaniti I . Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice. Nature. 2021; 593(7859):424-428. DOI: 10.1038/s41586-021-03461-y. View

17.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

18.

Chakraborty C, Bhattacharya M, Chopra H, Bhattacharya P, Islam M, Dhama K . Recently emerged omicron subvariant BF.7 and its R346T mutation in the RBD region reveal increased transmissibility and higher resistance to neutralization antibodies: need to understand more under the current scenario of rising cases in China and.... Int J Surg. 2023; 109(4):1037-1040. PMC: 10132299. DOI: 10.1097/JS9.0000000000000219. View

19.

Respaud R, Vecellio L, Diot P, Heuze-Vourch N . Nebulization as a delivery method for mAbs in respiratory diseases. Expert Opin Drug Deliv. 2015; 12(6):1027-39. DOI: 10.1517/17425247.2015.999039. View

20.

Pan Y, Wang L, Feng Z, Xu H, Li F, Shen Y . Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis. Lancet. 2023; 401(10377):664-672. PMC: 9949854. DOI: 10.1016/S0140-6736(23)00129-0. View