tetano
Editor, Senior Moderator
Med Microbiol Immunol
. 2024 Nov 9;213(1):24.
doi: 10.1007/s00430-024-00809-9. Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses
Fangfang Chang[SUP] #[/SUP][SUP] 1 [/SUP], Qian Wu[SUP] #[/SUP][SUP] 1 [/SUP], Yabin Hu[SUP] 2 [/SUP], Zhendong Pan[SUP] 3 [/SUP], Yong-Chen Liu[SUP] 1 [/SUP], Yue-Zhou Li[SUP] 1 [/SUP], Mihnea Bostina[SUP] 4 [/SUP], Wenpei Liu[SUP] 5 [/SUP], Ping Zhao[SUP] 6 [/SUP], Xiaowang Qu[SUP] 7 [/SUP], Yi-Ping Li[SUP] 8 [/SUP]
Affiliations
The concern of COVID-19 persists due to the continuous emergence of variants and the potential spillover of animal coronaviruses. The broad-spectrum neutralizing antibodies play a pivotal role in the prevention and treatment of coronavirus (CoV) infections. Here, we constructed 18 bi-specific antibodies (bsAbs) using 9 antibodies isolated from COVID-19 convalescents and vaccinated individuals, designed as dual variable domain immunoglobulin (DVD-Ig). A bsAb 5-HI showed a high binding capability to the S1 subunit of spike and exhibited breadth and potency against pseudotyped SARS-CoV-2 variants of concerns (VOCs) and SARS-related-CoVs (SARSr-CoVs), with half maximal effective concentration (EC[SUB]50[/SUB]) of 0.028-3.444 nM and 50% inhibitory concentration (IC[SUB]50[/SUB]) of 0.008-0.800 nM. In addition, it retained neutralization potency against the peudotyped virus of recently prevalent JN.1 strain (IC[SUB]50[/SUB], 12.74 nM). We found that the parental antibodies showed weak or no binding to the receptor binding domain (RBD) of the SARS-CoV, EG.5.1, and JN.1. However, the 5-HI maintained the binding with RBD and prevented the binding between hACE2 and RBD (IC[SUB]50[/SUB] for the RBD of SARS-CoV, 1.067 nM; EG.5.1, 0.423 nM; JN.1, 0.223 nM). In neutralization assays with the authentic virus, we found that the 5-HI effectively neutralized Omicron variants XBB.1.5 (IC[SUB]50[/SUB], 0.308 nM), EG.5.1 (IC[SUB]50[/SUB], 0.129 nM), and JN.1 (IC[SUB]50[/SUB], 13.692 nM), while its parental antibodies showed weakened or no neutralization. Therefore, the 5-HI represents a promising candidate for further development in the treatment and prevention of ongoing evolved SARS-CoV-2 VOCs and other SARSr-CoVs that potentially emerge in the future.
Keywords: SARS-CoV-2; SARSr-CoVs; bi-specific antibody (bsAb); monoclonal antibody (mAb); variants of concerns (VOCs).
. 2024 Nov 9;213(1):24.
doi: 10.1007/s00430-024-00809-9. Engineered bispecific antibodies with enhanced breadth and potency against SARS-CoV-2 variants and SARS-related coronaviruses
Fangfang Chang[SUP] #[/SUP][SUP] 1 [/SUP], Qian Wu[SUP] #[/SUP][SUP] 1 [/SUP], Yabin Hu[SUP] 2 [/SUP], Zhendong Pan[SUP] 3 [/SUP], Yong-Chen Liu[SUP] 1 [/SUP], Yue-Zhou Li[SUP] 1 [/SUP], Mihnea Bostina[SUP] 4 [/SUP], Wenpei Liu[SUP] 5 [/SUP], Ping Zhao[SUP] 6 [/SUP], Xiaowang Qu[SUP] 7 [/SUP], Yi-Ping Li[SUP] 8 [/SUP]
Affiliations
- PMID: 39520579
- DOI: 10.1007/s00430-024-00809-9
The concern of COVID-19 persists due to the continuous emergence of variants and the potential spillover of animal coronaviruses. The broad-spectrum neutralizing antibodies play a pivotal role in the prevention and treatment of coronavirus (CoV) infections. Here, we constructed 18 bi-specific antibodies (bsAbs) using 9 antibodies isolated from COVID-19 convalescents and vaccinated individuals, designed as dual variable domain immunoglobulin (DVD-Ig). A bsAb 5-HI showed a high binding capability to the S1 subunit of spike and exhibited breadth and potency against pseudotyped SARS-CoV-2 variants of concerns (VOCs) and SARS-related-CoVs (SARSr-CoVs), with half maximal effective concentration (EC[SUB]50[/SUB]) of 0.028-3.444 nM and 50% inhibitory concentration (IC[SUB]50[/SUB]) of 0.008-0.800 nM. In addition, it retained neutralization potency against the peudotyped virus of recently prevalent JN.1 strain (IC[SUB]50[/SUB], 12.74 nM). We found that the parental antibodies showed weak or no binding to the receptor binding domain (RBD) of the SARS-CoV, EG.5.1, and JN.1. However, the 5-HI maintained the binding with RBD and prevented the binding between hACE2 and RBD (IC[SUB]50[/SUB] for the RBD of SARS-CoV, 1.067 nM; EG.5.1, 0.423 nM; JN.1, 0.223 nM). In neutralization assays with the authentic virus, we found that the 5-HI effectively neutralized Omicron variants XBB.1.5 (IC[SUB]50[/SUB], 0.308 nM), EG.5.1 (IC[SUB]50[/SUB], 0.129 nM), and JN.1 (IC[SUB]50[/SUB], 13.692 nM), while its parental antibodies showed weakened or no neutralization. Therefore, the 5-HI represents a promising candidate for further development in the treatment and prevention of ongoing evolved SARS-CoV-2 VOCs and other SARSr-CoVs that potentially emerge in the future.
Keywords: SARS-CoV-2; SARSr-CoVs; bi-specific antibody (bsAb); monoclonal antibody (mAb); variants of concerns (VOCs).