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Viruses
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Antibody-Based Therapeutics and Diagnostics for Viral Diseases
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Antibody-Based Therapeutics and Diagnostics for Viral Diseases

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 7527

Special Issue Editor

Prof. Dr. Sukmook Lee

E-Mail Website1 Website2
Guest Editor
1. Antibody Research Institute, Kookmin University, Seoul 02707, Republic of Korea
2. Innovative Antibodies Laboratory, Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul 02707, Republic of Korea
Interests: cancer immunotherapy; chimeric antigen receptor T cells; bispecific antibodies; single domain antibody; virus therapy and diagnosis

Special Issue Information

Dear Colleagues,

Monoclonal antibodies (mAbs) are useful tools for the diagnosis and treatment of a variety of viral diseases induced by pre-existing and/or emerging viruses, including SARS-CoV, MERS, SARS-CoV-2, and HIV. Traditionally, the consecutive processes of immunization and hybridoma technology to produce a hybrid cell have been used to identify and overproduce target-specific mAbs. Recent advances in recombinant DNA technology have enabled antibody humanization, the generation of human naïve or synthetic antibody libraries, phage display antibody selection, and overproduction of phage-display-derived mAbs. Currently, despite the recent development of various antibody-based therapeutics and diagnostics for viral diseases, the accumulation of high-frequency mutations in viruses has often weakened the virus neutralization and detection activity of existing viral-protein-specific mAbs. In this Special Issue, we focus on covering novel antibody-based diagnostics and therapeutics including antibodies, nanobodies, aptamers, peptides, and Fc-fusion proteins for timely measures and effective management against viral diseases.

Prof. Dr. Sukmook Lee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • monoclonal antibody
  • bi-/multi-specific antibody
  • therapeutics
  • diagnostics
  • coronaviruses including SEAR-CoV, MERS-CoV, and SARS-CoV-2
  • viral diseases
  • platform technology

Published Papers (6 papers)

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Research

22 pages, 946 KiB  
Article
Design and Development of an Antigen Test for SARS-CoV-2 Nucleocapsid Protein to Validate the Viral Quality Assurance Panels
by Partha Ray, Melissa Ledgerwood-Lee, Howard Brickner, Alex E. Clark, Aaron Garretson, Rishi Graham, Westley Van Zant, Aaron F. Carlin and Eliah S. Aronoff-Spencer
Viruses 2024, 16(5), 662; https://doi.org/10.3390/v16050662 - 24 Apr 2024
Abstract
The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for the calibration and quality assurance of inactivated SARS-CoV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical [...] Read more.
The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for the calibration and quality assurance of inactivated SARS-CoV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. A heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-CoV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprised of UV-inactivated SARS-CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (limit of detection: 1.72–8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a 20 amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates. Full article
(This article belongs to the Special Issue Antibody-Based Therapeutics and Diagnostics for Viral Diseases)
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9 pages, 523 KiB  
Article
Development of an Immunochromatography Assay to Detect Marburg Virus and Ravn Virus
by Katendi Changula, Masahiro Kajihara, Shino Muramatsu, Koji Hiraoka, Toru Yamaguchi, Yoko Yago, Daisuke Kato, Hiroko Miyamoto, Akina Mori-Kajihara, Asako Shigeno, Reiko Yoshida, Corey W. Henderson, Andrea Marzi and Ayato Takada
Viruses 2023, 15(12), 2349; https://doi.org/10.3390/v15122349 - 29 Nov 2023
Viewed by 1125
Abstract
The recent outbreaks of Marburg virus disease (MVD) in Guinea, Ghana, Equatorial Guinea, and Tanzania, none of which had reported previous outbreaks, imply increasing risks of spillover of the causative viruses, Marburg virus (MARV) and Ravn virus (RAVV), from their natural host animals. [...] Read more.
The recent outbreaks of Marburg virus disease (MVD) in Guinea, Ghana, Equatorial Guinea, and Tanzania, none of which had reported previous outbreaks, imply increasing risks of spillover of the causative viruses, Marburg virus (MARV) and Ravn virus (RAVV), from their natural host animals. These outbreaks have emphasized the need for the development of rapid diagnostic tests for this disease. Using monoclonal antibodies specific to the viral nucleoprotein, we developed an immunochromatography (IC) assay for the rapid diagnosis of MVD. The IC assay was found to be capable of detecting approximately 102−4 50% tissue culture infectious dose (TCID50)/test of MARV and RAVV in the infected culture supernatants. We further confirmed that the IC assay could detect the MARV and RAVV antigens in the serum samples from experimentally infected nonhuman primates. These results indicate that the IC assay to detect MARV can be a useful tool for the rapid point-of-care diagnosis of MVD. Full article
(This article belongs to the Special Issue Antibody-Based Therapeutics and Diagnostics for Viral Diseases)
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15 pages, 1104 KiB  
Article
Effect of Different Levels of Maternally Derived Genotype VII Newcastle Disease Virus-Specific Hemagglutination Inhibition Antibodies on Protection against Virulent Challenge in Chicks
by Mei Liu, Xinyue Shen, Yan Yu, Jianmei Li, Jianhua Fan, Xuebo Jia and Yabin Dai
Viruses 2023, 15(9), 1840; https://doi.org/10.3390/v15091840 - 30 Aug 2023
Viewed by 915
Abstract
Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is an acute, highly contagious, and economically significant avian disease worldwide. Vaccination is the most effective measure for controlling ND. In recent years, vaccines matched with the prevalent strains of genotype VII [...] Read more.
Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is an acute, highly contagious, and economically significant avian disease worldwide. Vaccination is the most effective measure for controlling ND. In recent years, vaccines matched with the prevalent strains of genotype VII have been developed and are now commercially available. These vaccines can provide full protection for chickens against clinical disease and mortality after challenges with genotype VII viruses and significantly decrease virus shedding compared to conventional vaccines belonging to genotypes I and II. Vaccinated hens can transfer antibodies to their offspring through the egg yolk. Maternally derived antibodies can provide passive protection against diseases but can also interfere with vaccination efficacy early in life. This study was conducted on chicks hatched from hens vaccinated with a commercial genotype VII NDV-matched vaccine to investigate the correlation between hemagglutination inhibition (HI) antibody levels in chicks and hens and the decaying pattern of maternally derived HI antibodies, and to evaluate the protective efficacy of different levels of maternally derived HI antibodies against challenge with a virulent NDV strain of genotype VII based on survivability and virus shedding. The HI antibody titers in chicks at hatching were about 1.3 log2 lower than those in hens, indicating an antibody transfer rate of approximately 41.52%. The estimated half-life of these antibodies was about 3.2 days. The protective efficacy of maternally derived HI antibodies was positively correlated with the titer. These antibodies could effectively protect chicks against mortality when the titer was 7 log2 or higher, but they were unable to prevent virus shedding or infection even at a high titer of 11 log2. The obtained results will greatly assist producers in determining the immune status of chicks and formulating appropriate vaccination schedules against ND. Full article
(This article belongs to the Special Issue Antibody-Based Therapeutics and Diagnostics for Viral Diseases)
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12 pages, 3102 KiB  
Article
Visual and Super-Sensitive Detection of Maize Chlorotic Mottle Virus by Dot-ELISA and Au Nanoparticle-Based Immunochromatographic Test Strip
by Cui Zhang, Mengmeng Guo, Jinxi Dong, Li Liu, Xueping Zhou and Jianxiang Wu
Viruses 2023, 15(7), 1607; https://doi.org/10.3390/v15071607 - 22 Jul 2023
Cited by 2 | Viewed by 1236
Abstract
Maize chlorotic mottle virus (MCMV) is the only species in the Mahromovirus genus and is often co-infected with one or several viruses of the Potyvirus genus, posing a great threat to the global maize industry. Effective viral integrated management measures are dependent on [...] Read more.
Maize chlorotic mottle virus (MCMV) is the only species in the Mahromovirus genus and is often co-infected with one or several viruses of the Potyvirus genus, posing a great threat to the global maize industry. Effective viral integrated management measures are dependent on the timely and proper detection of the causal agent of the disease. In this work, six super-sensitive and specific monoclonal antibodies (mAbs) against MCMV were first prepared using purified MCMV virions as the immunogen. Then, the Dot enzyme-linked immunosorbent assay (Dot-ELISA) was established based on the obtained mAbs, and it can detect MCMV in infected maize leaf crude extracts diluted up to 1:10,240-fold (w/v, g/mL). Furthermore, a rapid and user-friendly Au nanoparticle-based immunochromatographic test strip (AuNP-ICTS) based on paired mAbs 7B12 and 17C4 was created for monitoring MCMV in point-of-care tests, and it can detect the virus in a 25,600-fold dilution (w/v, g/mL) of MCMV-infected maize leaf crude extracts. The whole test process for ICTS was completed in 10 min. Compared with conventional reverse transcription-polymerase chain reaction (RT-PCR), the detection endpoint of both serological methods is higher than that of RT-PCR, especially the Dot-ELISA, which is 12.1 times more sensitive than that of RT-PCR. In addition, the detection results of 20 blinded maize samples by the two serological assays were consistent with those of RT-PCR. Therefore, the newly created Dot-ELISA and AuNP-ICTS exhibit favorable application potential for the detection of MCMV in plant samples. Full article
(This article belongs to the Special Issue Antibody-Based Therapeutics and Diagnostics for Viral Diseases)
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11 pages, 1436 KiB  
Article
Reduced Binding between Omicron B.1.1.529 and the Human ACE2 Receptor in a Surrogate Virus Neutralization Test for SARS-CoV-2
by Tove Hoffman, Linda Kolstad, Dario Akaberi, Josef D. Järhult, Bengt Rönnberg and Åke Lundkvist
Viruses 2023, 15(6), 1280; https://doi.org/10.3390/v15061280 - 30 May 2023
Viewed by 2313
Abstract
The current gold standard assay for detecting neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the conventional virus neutralization test (cVNT), which requires infectious virus and a biosafety level 3 laboratory. Here, we report the development of a SARS-CoV-2 [...] Read more.
The current gold standard assay for detecting neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the conventional virus neutralization test (cVNT), which requires infectious virus and a biosafety level 3 laboratory. Here, we report the development of a SARS-CoV-2 surrogate virus neutralization test (sVNT) that, with Luminex technology, detects NAbs. The assay was designed to mimic the virus–host interaction and is based on antibody blockage between the human angiotensin-converting enzyme 2 (hACE2) receptor and the spike (S) protein of the Wuhan, Delta, and Omicron (B.1.1.529) variants of SARS-CoV-2. The sVNT proved to have a 100% correlation with a SARS-CoV-2 cVNT regarding qualitative results. Binding between the hACE2 receptor and the S1 domain of the B.1.1.529 lineage of the Omicron variant was not observed in the assay but between the receptor and an S1 + S2 trimer and the receptor binding domain (RBD) in a reduced manner, suggesting less efficient receptor binding for the B.1.1.529 Omicron variant. The results indicate that the SARS-CoV-2 sVNT is a suitable tool for both the research community and the public health service, as it may serve as an efficient diagnostic alternative to the cVNT. Full article
(This article belongs to the Special Issue Antibody-Based Therapeutics and Diagnostics for Viral Diseases)
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11 pages, 2397 KiB  
Article
Construction of a Hantaan Virus Phage Antibody Library and Screening for Potential Neutralizing Activity
by Zhuo Li, Huiyuan Zhang, Xiaxia Yu, Yusi Zhang and Lihua Chen
Viruses 2023, 15(5), 1034; https://doi.org/10.3390/v15051034 - 23 Apr 2023
Viewed by 1258
Abstract
China is one of the main epidemic areas for hemorrhagic fever with renal syndrome (HFRS). Currently, there is no human antibody specific to Hantaan virus (HTNV) for the emergency prevention and treatment of HFRS. To prepare human antibodies with neutralizing activity, we established [...] Read more.
China is one of the main epidemic areas for hemorrhagic fever with renal syndrome (HFRS). Currently, there is no human antibody specific to Hantaan virus (HTNV) for the emergency prevention and treatment of HFRS. To prepare human antibodies with neutralizing activity, we established an anti-HTNV phage antibody library using phage display technology by transforming peripheral blood mononuclear cells (PBMCs) of patients with HFRS into B lymphoblastoid cell lines (BLCLs) and extracting cDNA from BLCLs that secreted neutralizing antibodies. Based on the phage antibody library, we screened HTNV-specific Fab antibodies with neutralizing activities. Our study provides a potential way forward for the emergency prevention of HTNV and specific treatment of HFRS. Full article
(This article belongs to the Special Issue Antibody-Based Therapeutics and Diagnostics for Viral Diseases)
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