Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants

Jia Lu; Qiangling Yin; Rongjuan Pei; Qiu Zhang; Yuanyuan Qu; Yongbing Pan; Lina Sun; Ding Gao; Cuiqin Liang; Jingwen Yang; Wei Wu; Jiandong Li; Zongqiang Cui; Zejun Wang; Xinguo Li; Dexin Li; Shiwen Wang; Kai Duan; Wuxiang Guan; Mifang Liang; Xiaoming Yang

doi:10.1016/j.virs.2022.02.005

April 2022

Jia Lu, Qiangling Yin, Rongjuan Pei, Qiu Zhang, Yuanyuan Qu, Yongbing Pan, Lina Sun, Ding Gao, Cuiqin Liang, Jingwen Yang, Wei Wu, Jiandong Li, Zongqiang Cui, Zejun Wang, Xinguo Li, Dexin Li, Shiwen Wang, Kai Duan, Wuxiang Guan, Mifang Liang and Xiaoming Yang. Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants[J]. Virologica Sinica, 2022, 37(2): 238-247. doi: 10.1016/j.virs.2022.02.005

Citation: Jia Lu, Qiangling Yin, Rongjuan Pei, Qiu Zhang, Yuanyuan Qu, Yongbing Pan, Lina Sun, Ding Gao, Cuiqin Liang, Jingwen Yang, Wei Wu, Jiandong Li, Zongqiang Cui, Zejun Wang, Xinguo Li, Dexin Li, Shiwen Wang, Kai Duan, Wuxiang Guan, Mifang Liang, Xiaoming Yang. Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants .VIROLOGICA SINICA, 2022, 37(2) : 238-247. http://dx.doi.org/10.1016/j.virs.2022.02.005

广谱中和抗体鼻内给药可保护小鼠免受SARS-CoV-2 Delta和Omicron变异株的致命攻击

卢佳 ^a ,
殷强玲 ^b ,
裴荣娟 ^c,d ,
张秋 ^a ,
曲园园 ^e ,
潘勇兵 ^a ,
孙丽娜 ^b ,
高丁 ^c ,
梁翠琴 ^c ,
杨靖雯 ^c ,
芜为 ^b ,
李建东 ^b ,
崔中强 ^c ,
王泽鋆 ^a ,
李新国 ^a ,
李德新 ^b,d ,
王世文 ^b,d ,
段凯 ^a ,
关武祥 ^c,d,, ,
梁米芳 ^b,d,, ,
杨晓明 ^a,,

1 国家联合疫苗工程技术研究中心, 武汉生物制品研究所有限责任公司, 湖北武汉 430070
2 中国疾病预防控制中心病毒病预防控制所, 分子病毒学与基因工程国家重点实验室, 北京 102206
3 中国科学院武汉病毒学研究所新发传染病研究中心, 湖北武汉 430071
4 中国疾病预防控制中心-武汉病毒研究所新发疾病与生物安全联合研究中心, 武汉 430071
5 深圳湾实验室传染病研究所, 深圳 518107

通讯作者： 关武祥, guanwx@wh.iov.cn; 梁米芳, liangmf@ivdc.chinacdc.cn; 杨晓明, yangxiaoming@sinopharm.com
收稿日期： 2022-01-23
录用日期： 2022-02-16

摘要

SARS-CoV-2的多种新的变异株不断出现，如delta和omicron变异株，对目前已获得的中和抗体产生了耐药性。是否迫切需要发现新的治疗药物来对抗变异株。尽管已经有针对COVID-19的疫苗，但广谱中和抗体的使用被认为是预防或治疗SARS-Cov-2变异株感染的替代方法。在这项研究中，研究人员发现，鼻内给与两种之前被认为具有广谱中和活性的抗体(F61和H121)可以保护K18-hACE2小鼠免受SARS-CoV-2变异株的致命攻击。F61单独用药或F61/F121联合使用对200或1000 TCID50剂量的野生毒株(WIV04)和多种变异株(包括beta (B.1.351)、delta (B.1.617.2)、和omicron (B.1.1.529) 的广泛保护效力得到了验证。同时对delta和omicron的挑战的最低抗体给药剂量(5-1.25 mg/kg体重)也进行了评估。当给与20 mg/kg F61和F61/H121时，所有攻毒组均有充分的预防保护作用，相应小鼠肺病毒RNA呈阴性，肺泡间隔和空腔几乎全部正常。此外，低剂量抗体治疗对delta和omicron变异的致命攻击产生了显著的预防性保护，而F61/H121联合治疗对omicron感染表现出良好的效果。我们的研究结果表明，广谱单克隆中和抗体可用于预防和治疗当前出现的SARS-CoV-2变异株感染。
- 新冠肺炎
- , 新型冠状病毒
- , 预防保护
- , Omicron 变异株
- , K18-hACE2小鼠

Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants

Jia Lu ^a ,
Qiangling Yin ^b ,
Rongjuan Pei ^c,d ,
Qiu Zhang ^a ,
Yuanyuan Qu ^e ,
Yongbing Pan ^a ,
Lina Sun ^b ,
Ding Gao ^c ,
Cuiqin Liang ^c ,
Jingwen Yang ^c ,
Wei Wu ^b ,
Jiandong Li ^b ,
Zongqiang Cui ^c ,
Zejun Wang ^a ,
Xinguo Li ^a ,
Dexin Li ^b,d ,
Shiwen Wang ^b,d ,
Kai Duan ^a ,
Wuxiang Guan ^c,d,, ,
Mifang Liang ^b,d,, ,
Xiaoming Yang ^a,,

a National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd., Wuhan, 430070, China
b State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China
c Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
d CDC-WIV Joint Research Center for Emerging Diseases and Biosafety, Wuhan, 430071, China
e Institution of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, 518107, China

Corresponding author: Wuxiang Guan, guanwx@wh.iov.cn Mifang Liang, liangmf@ivdc.chinacdc.cn Xiaoming Yang, yangxiaoming@sinopharm.com
Received Date: 23 January 2022
Accepted Date: 16 February 2022

Abstract

Multiple new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have constantly emerged, as the delta and omicron variants, which have developed resistance to currently gained neutralizing antibodies. This highlights a critical need to discover new therapeutic agents to overcome the variants mutations. Despite the availability of vaccines against coronavirus disease 2019 (COVID-19), the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection. Here, we show that the nasal delivery of two previously characterized broadly neutralizing antibodies (F61 and H121) protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants. The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain (WIV04) and multiple variants, including beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) at 200 or 1000 TCID50, and the minimum antibody administration doses (5-1.25 mg/kg body weight) were also evaluated with delta and omicron challenge. Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight, and corresponding mice lung viral RNA showed negative, with almost all alveolar septa and cavities remaining normal. Furthermore, low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants, whereas the F61/H121 combination showed excellent results against omicron infection. Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.
- Coronavirus disease 2019 (COVID-2019)
- , Severe acute respiratory syndrome coronavirus 2
- , (SARS-CoV-2)
- , Prophylactic protection
- , Omicron variant

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