A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

Yuan, Mengqi; Chen, X.; Zhu, Yanzhi; Dong, Xiaoqing; Liu, Yan; Qian, Zhaohui; Ye, Lilin; Liu, Pinghuang

doi:10.1128/jvi.00775-22

Cited by 22 publications

(20 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this, intranasal vaccines were shown to induce a superior mucosal immunity in animal models, leading to higher protecting immunity against SARS-CoV-2 [ 30 , 31 , 32 ]. Moreover, broadly neutralizing IgA antibodies in mucosal tissues were reported to neutralize SARS-CoV-2 variants including Omicron [ 24 , 33 , 34 ]. Last, antibody-dependent enhancement (ADE), a phenomenon capable of facilitating virus entry and pathogenesis, has mainly observed with IgG rather than IgA through the FcγR involvement [ 35 ]; thus, a potent mucosal IgA response would be mainly protective.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Anti-SARS-CoV-2 IgA Response in Tears of Vaccinated COVID-19 Subjects

Soffritti

D’Accolti

Gallenga

et al. 2023

Viruses

View full text Add to dashboard Cite

Secretory IgA (sIgA), which may play an important role in the early defense against SARS-CoV-2 infection, were detected in the eye of COVID-19 patients. However, an evaluation of the sIgA response in the tears of vaccinated or non-vaccinated COVID-19 subjects is still lacking. Aimed at characterizing sIgA mucosal immunity in the eye, this study analyzed tear samples from 77 COVID-19 patients, including 63 vaccinated and 14 non-vaccinated subjects. The groups showed similar epidemiological features, but as expected, differences were observed in the percentage of asymptomatic/pauci-symptomatic subjects in the vaccinated vs. non-vaccinated cohort (46% and 29% of the total, respectively). Consistent with this, ocular sIgA values, evaluated by a specific quantitative ELISA assay, were remarkably different in vaccinated vs. non-vaccinated group for both frequency (69.8% vs. 57.1%, respectively) and titer (1372.3 U/ml vs. 143.7 U/ml, respectively; p = 0.01), which was significantly differently elevated depending on the type of administered vaccine. The data show for the first time significant differences of available vaccines to elicit sIgA response in the eye and suggest that quantitative tear-based sIgA tests may potentially serve as a rapid and easily accessible biomarker for the assessment of the development of a protective mucosal immunity toward SARS-CoV-2.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of Anti-SARS-CoV-2 IgA Response in Tears of Vaccinated COVID-19 Subjects

Soffritti

D’Accolti

Gallenga

et al. 2023

Viruses

View full text Add to dashboard Cite

show abstract

“…Another approach is to investigate different antibody formats, bispecific or multispecific, that can simultaneously and synergistically bind to multiple epitopes. [42][43][44][66][67][68][69][70][71][72][73] A study on bispecific antibodies combining anti-RBD and anti-S2 antibodies has been reported. 44 The structure of these bispecific antibodies involved a combination of scFvs from neutralizing antibodies against RBD and S2, arranged in tandem in the scFv-scFv-Fc format.…”

Section: Discussionmentioning

confidence: 99%

“…[42][43][44][66][67][68][69][70][71][72][73] A study on bispecific antibodies combining anti-RBD and anti-S2 antibodies has been reported. 44 The structure of these bispecific antibodies involved a combination of scFvs from neutralizing antibodies against RBD and S2, arranged in tandem in the scFv-scFv-Fc format. Unfortunately, the specific epitope targeted by the anti-S2 antibodies has not yet been described.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

Inoue,

Yamamoto,

Sato

et al. 2023

Preprint

View full text Add to dashboard Cite

A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue are bispecific antibodies which combine the targeting abilities of two antibodies with distinct epitopes. We engineered neutralizing bispecific antibodies in the IgG-scFv format from two initially non-neutralizing antibodies, CvMab-6 (which binds to the receptor-binding domain [RBD]) and CvMab-62 (targeting a spike protein S2 subunit epitope adjacent to the known anti-S2 antibody epitope). Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.

show abstract

“…Therefore, the development of a universal antibody is desired. Such antibodies have already been developed (4,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54) , (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70), but it is not known whether they have su cient neutralizing activity against the continuously emerging variants of omicron strains(4, 41-54) , (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70).…”

Section: Discussionmentioning

confidence: 99%

Rapid screening methods for universal binding peptide aptamers against SARS-CoV-2 variant spikes, including omicron variants, and their application to diagnostic and therapeutic agents.

Hayashi

2023

Preprint

View full text Add to dashboard Cite

The development of mRNA vaccines and oral drugs against SARS-CoV-2 has been useful in protecting against Covid-19 infection. Since then, however, many variants of delta and omicron strains with enhanced infectivity and immune escape capacity have emerged. A 7-amino acid random peptide ribosome display library screening system was used to perform a rapid in vitro screening of peptide aptamers that universally bind to the SARS-CoV-2 wild-type, delta, and Omicron variant BA.1, BA.2, and BA.5 spike RBD (Receptor Binding Domain). Screening resulted in four peptide aptamers that showed positive binding reactions in ELISA. Interestingly, Amino Acid Sequence Determination of the four clones predicted that three of the four clones contain 2 ~ 3 Cys residues in their sequences, forming a complex higher-order structure with disulfide (S-S) bonds. The 7-amino acid random peptide ribosome display library screening system allows for rapid in vitro screening of peptide aptamers that bind to other unknown emerging infectious disease pathogens that may be pandemic in the future. The peptide aptamers are as small as 30 amino acids and can be easily synthesized and purified as peptides or proteins, or simply used as mRNA drugs.

show abstract

A Bispecific Antibody Targeting RBD and S2 Potently Neutralizes SARS-CoV-2 Omicron and Other Variants of Concern

Cited by 22 publications

References 59 publications

Evaluation of Anti-SARS-CoV-2 IgA Response in Tears of Vaccinated COVID-19 Subjects

Evaluation of Anti-SARS-CoV-2 IgA Response in Tears of Vaccinated COVID-19 Subjects

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

Rapid screening methods for universal binding peptide aptamers against SARS-CoV-2 variant spikes, including omicron variants, and their application to diagnostic and therapeutic agents.

Contact Info

Product

Resources

About