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Viruses
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Therapeutic Antibodies against Virus Infection
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Therapeutic Antibodies against Virus Infection

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 (31 August 2023) | Viewed by 15637

Special Issue Editors

Dr. Adalbert Krawczyk

E-Mail Website
Guest Editor
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Duisburg-Essen, Essen, Germany
Interests: antiviral antibodies; vaccines; SARS-CoV-2; herpes simplex viruses; human cytomegalovirus; antiviral agents
Special Issues, Collections and Topics in MDPI journals
Dr. Matthias Zehner

E-Mail Website
Guest Editor
Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Interests: antibodies; viruses

Special Issue Information

Dear Colleagues,

Therapeutic monoclonal antibodies (mAbs) have become one of the fastest-growing classes of drugs in recent years and are approved for the treatment of a wide range of indications, including virus infections. Mabs and polyclonal antibodies are used for pre-exposure prophylaxis (Prep), post-exposure prophylaxis (PEP), and treatment of viral infections such as rabies, hepatitis B, SARS-CoV-2, RSV, and others.

Commonly, antibody-based immunotherapies are well-tolerated, highly specific, and thus potent tools to protect from infection or a severe course of disease.

Development, characterization, and pre-clinical or clinical evaluation of novel antiviral mAbs that can protect from disease is important, and articles on this topic are welcome.

Dr. Adalbert Krawczyk
Dr. Matthias Zehner
Guest Editors

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

  • antiviral antibodies
  • B cell response
  • convalescent plasma treatment
  • SARS-CoV-2
  • herpesviruses
  • HIV
  • ADCC
  • vaccines

Published Papers (7 papers)

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Research

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24 pages, 10137 KiB  
Article
SARS-CoV-2 Spike Protein Is Capable of Inducing Cell–Cell Fusions Independent from Its Receptor ACE2 and This Activity Can Be Impaired by Furin Inhibitors or a Subset of Monoclonal Antibodies
by Nina Reuter, Xiaohan Chen, Barbara Kropff, Antonia Sophia Peter, William J. Britt, Michael Mach, Klaus Überla and Marco Thomas
Viruses 2023, 15(7), 1500; https://doi.org/10.3390/v15071500 - 04 Jul 2023
Cited by 4 | Viewed by 1961
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was responsible for the COVID-19 pandemic, efficiently spreads cell-to-cell through mechanisms facilitated by its membrane glycoprotein spike. We established a dual split protein (DSP) assay based on the complementation of GFP and luciferase to quantify [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was responsible for the COVID-19 pandemic, efficiently spreads cell-to-cell through mechanisms facilitated by its membrane glycoprotein spike. We established a dual split protein (DSP) assay based on the complementation of GFP and luciferase to quantify the fusogenic activity of the SARS-CoV-2 spike protein. We provide several lines of evidence that the spike protein of SARS-CoV-2, but not SARS-CoV-1, induced cell–cell fusion even in the absence of its receptor, angiotensin-converting enzyme 2 (ACE2). This poorly described ACE2-independent cell fusion activity of the spike protein was strictly dependent on the proteasomal cleavage of the spike by furin while TMPRSS2 was dispensable. Previous and current variants of concern (VOCs) differed significantly in their fusogenicity. The Delta spike was extremely potent compared to Alpha, Beta, Gamma and Kappa, while the Omicron spike was almost devoid of receptor-independent fusion activity. Nonetheless, for all analyzed variants, cell fusion was dependent on furin cleavage and could be pharmacologically inhibited with CMK. Mapping studies revealed that amino acids 652-1273 conferred the ACE2-independent fusion activity of the spike. Unexpectedly, residues proximal to the furin cleavage site were not of major relevance, whereas residue 655 critically regulated fusion. Finally, we found that the spike’s fusion activity in the absence of ACE2 could be inhibited by antibodies directed against its N-terminal domain (NTD) but not by antibodies targeting its receptor-binding domain (RBD). In conclusion, our BSL-1-compatible DSP assay allowed us to screen for inhibitors or antibodies that interfere with the spike’s fusogenic activity and may therefore contribute to both rational vaccine design and development of novel treatment options against SARS-CoV-2. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
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12 pages, 1922 KiB  
Article
False-Positive Screening and Confirmatory HIV Diagnostic Test in a Patient with Cured SARS-CoV-2 Infection Is Not Mediated by Env/Spike Cross-Reactive Antibodies
by Carina Elsner, Gwenllian A. Appeltrath, Margarethe Konik, Janine Parreuter, Martina Broecker-Preuss, Adalbert Krawczyk, Stefan Esser, Stefanie Sammet and Christina B. Karsten
Viruses 2023, 15(5), 1161; https://doi.org/10.3390/v15051161 - 13 May 2023
Cited by 2 | Viewed by 4258
Abstract
Acute SARS-CoV-2 infection has been associated with false-positive HIV screening tests. The underlying mechanism is unclear, and for clinical cases, evidence beyond a temporal connection is missing. However, several experimental studies point toward SARS-CoV-2 spike/HIV-1 envelope (Env) cross-reactive antibodies (Abs) as a cause. [...] Read more.
Acute SARS-CoV-2 infection has been associated with false-positive HIV screening tests. The underlying mechanism is unclear, and for clinical cases, evidence beyond a temporal connection is missing. However, several experimental studies point toward SARS-CoV-2 spike/HIV-1 envelope (Env) cross-reactive antibodies (Abs) as a cause. Here, we present the first case of an individual with convalescent SARS-CoV-2 infection testing false positive in both an HIV screening and confirmatory test. Longitudinal sampling showed that the phenomenon was temporary but lasted for at least 3 months before waning. After excluding a multitude of common determinants for assay interference, we further show by antibody depletion studies that SARS-CoV-2-spike-specific Abs did not cross-react with HIV-1 gp120 in the patient sample. No additional case of HIV test interference was identified in a cohort of 66 individuals who presented to a post-COVID-19 outpatient clinic. We conclude the SARS-CoV-2-associated HIV test interference to be a temporary process capable of disturbing both screening and confirmatory assays. The assay interference is short-lived and/or rare but should be considered by physicians as a possible explanation for unexpected HIV diagnostic results in patients with a recent SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
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16 pages, 3696 KiB  
Article
Optimizing Antibody Affinity and Developability Using a Framework–CDR Shuffling Approach—Application to an Anti-SARS-CoV-2 Antibody
by Ranjani Gopal, Emmett Fitzpatrick, Niharika Pentakota, Akila Jayaraman, Kannan Tharakaraman and Ishan Capila
Viruses 2022, 14(12), 2694; https://doi.org/10.3390/v14122694 - 30 Nov 2022
Cited by 4 | Viewed by 2233
Abstract
The computational methods used for engineering antibodies for clinical development have undergone a transformation from three-dimensional structure-guided approaches to artificial-intelligence- and machine-learning-based approaches that leverage the large sequence data space of hundreds of millions of antibodies generated by next-generation sequencing (NGS) studies. Building [...] Read more.
The computational methods used for engineering antibodies for clinical development have undergone a transformation from three-dimensional structure-guided approaches to artificial-intelligence- and machine-learning-based approaches that leverage the large sequence data space of hundreds of millions of antibodies generated by next-generation sequencing (NGS) studies. Building on the wealth of available sequence data, we implemented a computational shuffling approach to antibody components, using the complementarity-determining region (CDR) and the framework region (FWR) to optimize an antibody for improved affinity and developability. This approach uses a set of rules to suitably combine the CDRs and FWRs derived from naturally occurring antibody sequences to engineer an antibody with high affinity and specificity. To illustrate this approach, we selected a representative SARS-CoV-2-neutralizing antibody, H4, which was identified and isolated previously based on the predominant germlines that were employed in a human host to target the SARS-CoV-2-human ACE2 receptor interaction. Compared to screening vast CDR libraries for affinity enhancements, our approach identified fewer than 100 antibody framework–CDR combinations, from which we screened and selected an antibody (CB79) that showed a reduced dissociation rate and improved affinity against the SARS-CoV-2 spike protein (7-fold) when compared to H4. The improved affinity also translated into improved neutralization (>75-fold improvement) of SARS-CoV-2. Our rapid and robust approach for optimizing antibodies from parts without the need for tedious structure-guided CDR optimization will have broad utility for biotechnological applications. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
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19 pages, 2081 KiB  
Article
Cross-Reactive Fc-Fused Single-Domain Antibodies to Hemagglutinin Stem Region Protect Mice from Group 1 Influenza a Virus Infection
by Daria V. Voronina, Dmitry V. Shcheblyakov, Irina A. Favorskaya, Ilias B. Esmagambetov, Alina S. Dzharullaeva, Amir I. Tukhvatulin, Olga V. Zubkova, Olga Popova, Vladislav Y. Kan, Alina S. Bandelyuk, Maxim M. Shmarov, Denis Y. Logunov, Boris S. Naroditskiy and Aleksandr L. Gintsburg
Viruses 2022, 14(11), 2485; https://doi.org/10.3390/v14112485 - 10 Nov 2022
Cited by 2 | Viewed by 1749
Abstract
The continued evolution of influenza viruses reduces the effectiveness of vaccination and antiviral drugs. The identification of novel and universal agents for influenza prophylaxis and treatment is an urgent need. We have previously described two potent single-domain antibodies (VHH), G2.3 and H1.2, which [...] Read more.
The continued evolution of influenza viruses reduces the effectiveness of vaccination and antiviral drugs. The identification of novel and universal agents for influenza prophylaxis and treatment is an urgent need. We have previously described two potent single-domain antibodies (VHH), G2.3 and H1.2, which bind to the stem domain of hemagglutinin and efficiently neutralize H1N1 and H5N2 influenza viruses in vivo. In this study, we modified these VHHs with Fc-fragment to enhance their antiviral activity. Reformatting of G2.3 into bivalent Fc-fusion molecule increased its in vitro neutralizing activity against H1N1 and H2N3 viruses up to 80-fold and, moreover, resulted in obtaining the ability to neutralize H5N2 and H9N2 subtypes. We demonstrated that a dose as low as 0.6 mg/kg of G2.3-Fc or H1.2-Fc administered systemically or locally before infection could protect mice from lethal challenges with both H1N1 and H5N2 viruses. Furthermore, G2.3-Fc reduced the lung viral load to an undetectable level. Both VHH-Fc antibodies showed in vivo therapeutic efficacy when delivered via systemic or local route. The findings support G2.3-Fc as a potential therapeutic agent for both prophylaxis and therapy of Group 1 influenza A infection. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
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Review

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25 pages, 1304 KiB  
Review
Development of Therapeutic Monoclonal Antibodies for Emerging Arbovirus Infections
by Leonardo F. Ormundo, Carolina T. Barreto and Lilian R. Tsuruta
Viruses 2023, 15(11), 2177; https://doi.org/10.3390/v15112177 - 30 Oct 2023
Viewed by 1421
Abstract
Antibody-based passive immunotherapy has been used effectively in the treatment and prophylaxis of infectious diseases. Outbreaks of emerging viral infections from arthropod-borne viruses (arboviruses) represent a global public health problem due to their rapid spread, urging measures and the treatment of infected individuals [...] Read more.
Antibody-based passive immunotherapy has been used effectively in the treatment and prophylaxis of infectious diseases. Outbreaks of emerging viral infections from arthropod-borne viruses (arboviruses) represent a global public health problem due to their rapid spread, urging measures and the treatment of infected individuals to combat them. Preparedness in advances in developing antivirals and relevant epidemiological studies protect us from damage and losses. Immunotherapy based on monoclonal antibodies (mAbs) has been shown to be very specific in combating infectious diseases and various other illnesses. Recent advances in mAb discovery techniques have allowed the development and approval of a wide number of therapeutic mAbs. This review focuses on the technological approaches available to select neutralizing mAbs for emerging arbovirus infections and the next-generation strategies to obtain highly effective and potent mAbs. The characteristics of mAbs developed as prophylactic and therapeutic antiviral agents for dengue, Zika, chikungunya, West Nile and tick-borne encephalitis virus are presented, as well as the protective effect demonstrated in animal model studies. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
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Other

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8 pages, 242 KiB  
Case Report
Rational Use of Monoclonal Antibodies as Therapeutic Treatment in an Oncologic Patient with Long COVID
by Maria Grazia Cusi, Anna Maria Di Giacomo, Gabriele Anichini, Gianni Gori Savellini, Chiara Terrosi, Claudia Gandolfo and Michele Maio
Viruses 2023, 15(3), 614; https://doi.org/10.3390/v15030614 - 23 Feb 2023
Viewed by 1520
Abstract
We present the case of a 76-year-old male patient persistently infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the setting of a stage IIIC cutaneous melanoma and non-Hodgkin’s lymphoma (NHL). Due to the persistent coronavirus disease 19 (COVID-19), all cancer treatments [...] Read more.
We present the case of a 76-year-old male patient persistently infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the setting of a stage IIIC cutaneous melanoma and non-Hodgkin’s lymphoma (NHL). Due to the persistent coronavirus disease 19 (COVID-19), all cancer treatments were discontinued. Because of the worsening of his clinical state and the persistence of SARS-CoV-2 positivity for more than six months, the patient was treated with sotrovimab, which was ineffective due to resistance mutations acquired during that time. In order to resume cancer treatment and make the patient free from SARS-CoV-2, an in vitro screening of Evusheld monoclonal antibodies (tixagevumab–cilgavimab) against the viral strains isolated from the subject was performed. The promising results obtained during in vitro testing led to the authorization of the off-label use of Evusheld, which made the patient negative for SARS-CoV-2, thus, allowing him to resume his cancer treatment. This study highlights the Evusheld monoclonal antibodies’ efficacy, not only in prevention but also in successful therapy against prolonged COVID-19. Therefore, testing neutralizing monoclonal antibodies in vitro against SARS-CoV-2 mutants directly isolated from patients could provide useful information for the treatment of people affected by long COVID. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
9 pages, 259 KiB  
Brief Report
Effectiveness of Sotrovimab in the Omicron Storm Time: A Case Series
by Gaetano Cicchitto, Lorena Cardillo, Davide Sequino, Paola Sabatini, Luisa Adamo, Rosita Marchitiello, Maurizio Viscardi, Loredana Cozzolino, Antonietta Cavallera, Marialuisa Bocchino, Alessandro Sanduzzi Zamparelli, Francesco Ferrigno, Esterina de Carlo, Claudio de Martinis and Giovanna Fusco
Viruses 2023, 15(1), 102; https://doi.org/10.3390/v15010102 - 30 Dec 2022
Cited by 2 | Viewed by 1758
Abstract
Neutralizing monoclonal antibodies (mAbs) for pre- and post-exposure prophylaxis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are largely used to prevent the progression of the disease by blocking viral attachment, host cell entry, and infectivity. Sotrovimab, like other available mAbs, has been [...] Read more.
Neutralizing monoclonal antibodies (mAbs) for pre- and post-exposure prophylaxis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are largely used to prevent the progression of the disease by blocking viral attachment, host cell entry, and infectivity. Sotrovimab, like other available mAbs, has been developed against the receptor binding Domain of the Spike (S) glycoprotein of the virus. Nevertheless, the latest Omicron variant has shown marked mutations within the S gene, thus opening the question of the efficacy of these neutralizing molecules towards this novel variant. In the present observational study, we describe the effects of Sotrovimab in the treatment of 15 fully vaccinated patients, infected by SARS-CoV-2 Omicron sub-variants, who were selected on the basis of factors widely considered to affect a worse prognosis: immune suppression (n = 12) and/or chronic kidney disease (n = 5) with evidence of interstitial pneumonia in nine patients. The effectiveness of Sotrovimab in the treatment of severe cases of COVID-19 was demonstrated by the regression of symptoms (mean 5.7 days), no need of hospitalisation, improvement of general health conditions and viral clearance within 30 days in all patients. In conclusion, although loss or reduction of mAbs neutralizing activity against the Omicron variant have been described, Sotrovimab has clinically proven to be a safe and useful treatment for patients with high risk of progression to severe COVID-19 infected by Omicron sub-variants. Full article
(This article belongs to the Special Issue Therapeutic Antibodies against Virus Infection)
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