Structure-guided antibody cocktail for prevention and treatment of COVID-19

Su, Shih-Chieh; Yang, Tzu-Jing; Yu, Pei-Yu; Liang, Kang-Hao; Chen, Wan‐Yu; Yang, Chun-Wei; Lin, Hsiu-Ting; Wang, Mei-Jung; Lu, Ruei‐Min; Tso, Hsien-Cheng; Chung, Meng-Jhe; Hsieh, Tzung-Yang; Chang, Yu‐Ling; Lin, Shin-Chang; Hsu, Fang‐Yu; Ke, Feng-Yi; Wu, Yi‐Hsuan; Hwang, Yu-Chyi; Liu, I-Ju; Liang, Jian-Jong; Liao, Chun-Che; Ko, Hui-Ying; Sun, Cheng‐Pu; Wu, Ping-Yi; Jan, Jia-Tsrong; Chang, Yuan-Chih; Lin, Yi-Ling; Tao, Mi‐Hua; Hsu, Shang‐Te Danny; Wu, Han‐Chung

doi:10.1371/journal.ppat.1009704

Cited by 14 publications

(25 citation statements)

References 69 publications

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“…This result suggested that besides RBD-chAb-25, most of our neutralizing Abs might retain activity against these VOCs. Our previous work showed that RBD-chAb-25 and -45 could simultaneously bind to the RBD of SARS-CoV-2 S protein using cryo-EM, and the combination exhibited a synergistic effect compared to single chAbs when used as a prophylactic treatment [ 39 ]. Therefore, we further examined the neutralizing abilities of our six most potent RBD-chAbs toward several SARS-CoV-2 variant pseudoviruses.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, we found that RBD-chAb-45 and -51 share overlapping epitopes according to an ELISA-based competition-binding assay [ 39 ]. In addition, RBD-chAb-15 and -28 have highly similar epitopes, and RBD-chAb-25 has an epitope that partially overlaps with those of RBD-chAb-15 and -28.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, RBD-chAb-15 and -28 have highly similar epitopes, and RBD-chAb-25 has an epitope that partially overlaps with those of RBD-chAb-15 and -28. However, only RBD-chAb-25 loses its neutralizing ability against SARS-CoV-2 variant pseudoviruses with the N501Y mutation [ 39 ]. To evaluate the neutralizing abilities of cocktails containing RBD-chAbs with different epitopes, we performed neutralization tests using SARS-CoV-2 variant pseudoviruses.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we generated six neutralizing chimeric Abs (chAbs) against the RBD of SARS-CoV-2 S protein, all of which exhibited potent neutralizing capabilities in vitro and in vivo. Furthermore, the prophylactic and therapeutic efficacies of these chAbs or antibody cocktails were confirmed in SARS-CoV-2-infected mouse and hamster models [ 38 , 39 ]. Variants of SARS-CoV-2 that carry mutations in the RBD could affect the binding and neutralizing abilities of our antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Antibody cocktail effective against variants of SARS-CoV-2

Liang

Chiang

et al. 2021

J Biomed Sci

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Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing antibodies. Methods We analyzed the binding activity of six highly potent antibodies to the spike proteins of SARS-CoV-2 variants, assessed their neutralizing abilities with pseudovirus and authentic SARS-CoV-2 variants and evaluate efficacy of antibody cocktail in Delta SARS-CoV-2-infected hamster models as prophylactic and post-infection treatments. Results The tested RBD-chAbs, except RBD-chAb-25, maintained binding ability to spike proteins from SARS-CoV-2 variants. However, only RBD-chAb-45 and -51 retained neutralizing activities; RBD-chAb-1, -15, -25 and -28 exhibited diminished neutralization for all SARS-CoV-2 variants. Notably, several cocktails of our antibodies showed low IC50 values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including United Kingdom variant B.1.1.7 (Alpha), South Africa variant B.1.351 (Beta), Brazil variant P1 (Gamma), California variant B.1.429 (Epsilon), New York variant B.1.526 (Iota), and India variants, B.1.617.1 (Kappa) and B.1.617.2 (Delta). RBD-chAb-45, and -51 showed PRNT50 values 4.93–37.54 ng/ml when used as single treatments or in combination with RBD-chAb-15 or -28, according to plaque assays with authentic Alpha, Gamma and Delta SARS-CoV-2 variants. Furthermore, the antibody cocktail of RBD-chAb-15 and -45 exhibited potent prophylactic and therapeutic effects in Delta SARS-CoV-2 variant-infected hamsters. Conclusions The cocktail of RBD-chAbs exhibited potent neutralizing activities against SARS-CoV-2 variants. These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibody cocktail effective against variants of SARS-CoV-2

Liang

Chiang

et al. 2021

J Biomed Sci

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“…Anti-NP mAbs were generated according to previously described procedures [43,44]. Female 4-6-week-old BALB/c mice were immunized with wild-type recombinant NP-His.…”

Section: Generation and Purification Of Mabsmentioning

confidence: 99%

Monoclonal Antibodies against Nucleocapsid Protein of SARS-CoV-2 Variants for Detection of COVID-19

Chen

et al. 2021

IJMS

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Mitigation strategies of the coronavirus disease 2019 (COVID-19) pandemic have been greatly hindered by the continuous emergence of SARS-CoV-2 variants. New sensitive, rapid diagnostic tests for the wide-spectrum detection of viral variants are needed. We generated a panel of 41 monoclonal antibodies against the SARS-CoV-2 nucleocapsid protein (NP) by using mice hybridoma techniques. Of these mAbs, nine exhibited high binding activities and were applied in latex-based lateral flow immunoassays (LFIAs). The LFIAs utilizing NP-mAb-7 and -40 had the best sensitivity and lowest limit of detection: 8 pg for purified NP and 625 TCID50/mL for the authentic virus (hCoV-19/Taiwan/4/2020). The specificity tests showed that the NP-mAb-40/7 LFIA strips did not cross-react with five human coronavirus strains or 20 other common respiratory pathogens. Importantly, we found that 10 NP mutants, including alpha (B.1.1.7), beta (B.1.351), gamma (P.1), and delta (B.1.617.2) variants, could be detected by NP-mAb-40/7 LFIA strips. A clinical study (n = 60) of the NP-mAb-40/7 LFIA strips demonstrated a specificity of 100% and sensitivity of 90% in infected individuals with cycle threshold (Ct) values < 29.5. These anti-NP mAbs have strong potential for use in the clinical detection of SARS-CoV-2 infection, whether the virus is wild-type or a variant of concern.

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Current clinical status of new COVID-19 vaccines and immunotherapy

Nagpal

Kaushik

et al. 2022

Environ Sci Pollut Res

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COVID-19, caused by SARS-CoV-2, is a positive-strand RNA belonging to Coronaviridae family, along with MERS and SARS . Since its first report in 2019 in Wuhan, China, it has affected over 530 million people and led to 6.3 million deaths worldwide until June 2022. Despite eleven vaccines being used worldwide already, new variants are of concern. Therefore, the governing bodies are re-evaluating the strategies for achieving universal vaccination. Initially, the WHO expected that vaccines showing around 50–80% efficacy would develop in 1–2 years. However, US-FDA announced emergency approval of the two m-RNA vaccines within 11 months of vaccine development, which enabled early vaccination for healthcare workers in many countries. Later, in January 2021, 63 vaccine candidates were under human clinical trials and 172 under preclinical development. Currently, the number of such clinical studies is still increasing. In this review, we have summarized the updates on the clinical status of the COVID-19 and the available treatments. Additionally, COVID-19 had created negative impacts on world’s economy; affected agriculture, industries, and tourism service sectors; and majorly affected low-income countries. The review discusses the clinical outcomes, latest statistics, socio-economic impacts of pandemic and treatment approaches against SARS-CoV-2, and strategies against the new variant of concern. The review will help understand the current status of vaccines and other therapies while also providing insights about upcoming vaccines and therapies for COVID-19 management. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11356-022-22661-1.

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Structure-guided antibody cocktail for prevention and treatment of COVID-19

Cited by 14 publications

References 69 publications

Antibody cocktail effective against variants of SARS-CoV-2

Antibody cocktail effective against variants of SARS-CoV-2

Monoclonal Antibodies against Nucleocapsid Protein of SARS-CoV-2 Variants for Detection of COVID-19

Current clinical status of new COVID-19 vaccines and immunotherapy

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