tetano
Editor, Senior Moderator
Virol Sin
. 2022 Feb 18;S1995-820X(22)00037-2.
doi: 10.1016/j.virs.2022.02.005. Online ahead of print.
Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants
Jia Lu[SUP] 1 [/SUP], Qiangling Yin[SUP] 2 [/SUP], Rongjuan Pei[SUP] 3 [/SUP], Qiu Zhang[SUP] 1 [/SUP], Yuanyuan Qu[SUP] 4 [/SUP], Yongbing Pan[SUP] 1 [/SUP], Lina Sun[SUP] 2 [/SUP], Ding Gao[SUP] 5 [/SUP], Cuiqin Liang[SUP] 5 [/SUP], Jingwen Yang[SUP] 5 [/SUP], Wei Wu[SUP] 2 [/SUP], Jiandong Li[SUP] 2 [/SUP], Zongqiang Cui[SUP] 5 [/SUP], Zejun Wang[SUP] 1 [/SUP], Xinguo Li[SUP] 1 [/SUP], Dexin Li[SUP] 6 [/SUP], Shiwen Wang[SUP] 6 [/SUP], Kai Duan[SUP] 1 [/SUP], Wuxiang Guan[SUP] 7 [/SUP], Mifang Liang[SUP] 8 [/SUP], Xiaoming Yang[SUP] 9 [/SUP]
Affiliations
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 TCID[SUB]50[/SUB], 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.
Keywords: Coronavirus disease 2019 (COVID-2019); K18-hACE2; Omicron variant; Prophylactic protection; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
. 2022 Feb 18;S1995-820X(22)00037-2.
doi: 10.1016/j.virs.2022.02.005. Online ahead of print.
Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants
Jia Lu[SUP] 1 [/SUP], Qiangling Yin[SUP] 2 [/SUP], Rongjuan Pei[SUP] 3 [/SUP], Qiu Zhang[SUP] 1 [/SUP], Yuanyuan Qu[SUP] 4 [/SUP], Yongbing Pan[SUP] 1 [/SUP], Lina Sun[SUP] 2 [/SUP], Ding Gao[SUP] 5 [/SUP], Cuiqin Liang[SUP] 5 [/SUP], Jingwen Yang[SUP] 5 [/SUP], Wei Wu[SUP] 2 [/SUP], Jiandong Li[SUP] 2 [/SUP], Zongqiang Cui[SUP] 5 [/SUP], Zejun Wang[SUP] 1 [/SUP], Xinguo Li[SUP] 1 [/SUP], Dexin Li[SUP] 6 [/SUP], Shiwen Wang[SUP] 6 [/SUP], Kai Duan[SUP] 1 [/SUP], Wuxiang Guan[SUP] 7 [/SUP], Mifang Liang[SUP] 8 [/SUP], Xiaoming Yang[SUP] 9 [/SUP]
Affiliations
- PMID: 35527227
- DOI: 10.1016/j.virs.2022.02.005
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 TCID[SUB]50[/SUB], 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.
Keywords: Coronavirus disease 2019 (COVID-2019); K18-hACE2; Omicron variant; Prophylactic protection; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).