tetano
Editor, Senior Moderator
Heliyon
. 2023 May;9(5):e15587.
doi: 10.1016/j.heliyon.2023.e15587. Epub 2023 Apr 18.
Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice
Ruei-Min Lu[SUP] 1 [/SUP], Kang-Hao Liang[SUP] 1 [/SUP], Hsiao-Ling Chiang[SUP] 1 [/SUP], Fu-Fei Hsu[SUP] 1 [/SUP], Hsiu-Ting Lin[SUP] 2 [/SUP], Wan-Yu Chen[SUP] 2 [/SUP], Feng-Yi Ke[SUP] 1 [/SUP], Monika Kumari[SUP] 2 [/SUP], Yu-Chi Chou[SUP] 1 [/SUP], Mi-Hua Tao[SUP] 1 3 [/SUP], Yi-Ling Lin[SUP] 1 3 [/SUP], Han-Chung Wu[SUP] 1 2 [/SUP]
Affiliations
Abstract
The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC[SUB]50[/SUB] values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.
Keywords: Antibody humanization; COVID-19; Neutralizing antibody; SARS-CoV-2; mRNA LNP.
. 2023 May;9(5):e15587.
doi: 10.1016/j.heliyon.2023.e15587. Epub 2023 Apr 18.
Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice
Ruei-Min Lu[SUP] 1 [/SUP], Kang-Hao Liang[SUP] 1 [/SUP], Hsiao-Ling Chiang[SUP] 1 [/SUP], Fu-Fei Hsu[SUP] 1 [/SUP], Hsiu-Ting Lin[SUP] 2 [/SUP], Wan-Yu Chen[SUP] 2 [/SUP], Feng-Yi Ke[SUP] 1 [/SUP], Monika Kumari[SUP] 2 [/SUP], Yu-Chi Chou[SUP] 1 [/SUP], Mi-Hua Tao[SUP] 1 3 [/SUP], Yi-Ling Lin[SUP] 1 3 [/SUP], Han-Chung Wu[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37090428
- PMCID: PMC10111857
- DOI: 10.1016/j.heliyon.2023.e15587
Abstract
The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC[SUB]50[/SUB] values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.
Keywords: Antibody humanization; COVID-19; Neutralizing antibody; SARS-CoV-2; mRNA LNP.