scholarly journals A review on monoclonal antibodies in COVID-19: Role in immunotherapy, vaccine development and viral detection

2021 ◽  
pp. 1-13
Author(s):  
Ashraf A. Tabll ◽  
Yasser E. Shahein ◽  
Mohamed M. Omran ◽  
Mostafa M. Elnakib ◽  
Ameera A. Ragheb ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Research Review ◽  
Human Monoclonal Antibodies ◽  
Viral Detection ◽  
Counter Measures ◽  
Treatment And Prevention ◽  
High Antiviral Activity

The harmful COVID-19 pandemic caused by the SARS-CoV-2 coronavirus imposes the scientific community to develop or find conventional curative drugs, protective vaccines, or passive immune strategies rapidly and efficiently. Passive immunity is based on recovering hyper-immune plasma from convalescent patients, or monoclonal antibodies with elevated titer of neutralizing antibodies with high antiviral activity, that have potential for both treatment and prevention. In this review, we focused on researching the potentiality of monoclonal antibodies for the prevention and treatment of COVID-19 infection. Our research review includes antibody-based immunotherapy, using human monoclonal antibodies targeting SARS-CoV-2 viral protein regions, specifically the spike protein regions, and using hyper-immune plasma from convalescent COVID-19 patients, in which monoclonal antibodies act as immunotherapy for the cytokine storm syndrome associated with the covid-19 infection. In addition, we will demonstrate the role of the monoclonal antibodies in the development of candidate vaccines for SARS-CoV-2. Moreover, the recent progress of the diagnostic mouse monoclonal antibodies’ role will be highlighted, as an accurate and rapid diagnostic assay, in the antigen detection of SARS-Cov-2. In brief, the monoclonal antibodies are the potential counter measures that may control SARS-CoV-2, which causes COVID-19 disease, through immunotherapy and vaccine development, as well as viral detection.

scholarly journals Fc-independent neutralization of SARS-CoV-2 by recombinant human monoclonal antibodies

2021 ◽  
Author(s):  
Tal Noy-Porat ◽  
Avishay Edri ◽  
Ron Alcalay ◽  
Efi Makdasi ◽  
David Gur ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Human Monoclonal Antibodies ◽  
Antibody Treatment ◽  
Effector Cells ◽  
Future Design ◽  
Endogenous Immune Response ◽  
The Complement System

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in vivo neutralization of SARS-CoV-2 is not yet clear. Delineating the role this process plays in antibody-mediated protection will have a great impact on the design of such therapeutics. Here, the Fc of two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, targeting distinct domains of the spike, was engineered to abrogate their Fc-dependent functions. The protective activity of these antibodies was tested against lethal SARS-CoV-2 infections in K18-hACE2 transgenic mice, both before or two days post-exposure in comparison to their original, Fc-active antibodies. Antibody treatment with both Fc-variants similarly rescued the mice from death, reduced viral load and prevented signs of morbidity. In addition, surviving animals developed a significant endogenous immune response towards the virus. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in antibody-mediated protection, which should aid in future design of effective antibody-based therapies.

scholarly journals Fc-Independent Protection from SARS-CoV-2 Infection by Recombinant Human Monoclonal Antibodies

Antibodies ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 45
Author(s):  
Tal Noy-Porat ◽  
Avishay Edri ◽  
Ron Alcalay ◽  
Efi Makdasi ◽  
David Gur ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Complement System ◽  
Neutralizing Antibodies ◽  
Human Monoclonal Antibodies ◽  
Antibody Treatment ◽  
Future Design ◽  
The Complement System

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity (in-vitro) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies.

scholarly journals Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
J. A. Swanstrom ◽  
J. A. Plante ◽  
K. S. Plante ◽  
E. F. Young ◽  
E. McGowan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dengue Virus ◽  
Pregnant Women ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Fetal Loss ◽  
Human Monoclonal Antibodies ◽  
Serum Dilution ◽  
Homologous Virus

ABSTRACT Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC 50 ], <1:100 serum dilution; 18%) or moderate to high (EC 50 , >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV. IMPORTANCE ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses.

scholarly journals Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody

2020 ◽  
Author(s):  
Ronit Rosenfeld ◽  
Tal Noy-Porat ◽  
Adva Mechaly ◽  
Efi Makdasi ◽  
Yinon Levy ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Transgenic Mice ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Human Monoclonal Antibody ◽  
Human Monoclonal Antibodies ◽  
Mortality And Morbidity ◽  
Life Saving ◽  
Therapeutic Value

AbstractCoronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human live, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterized and further evaluated the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. 75% of the untreated mice succumbed 6-9 days post-infection while administration of the MD65 antibody as late as 3 days after exposure, rescued all infected animals. The data unprecedentedly demonstrate, the therapeutic value of human monoclonal antibodies as a life-saving treatment of severe COVID-19 infection.

scholarly journals Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001

2016 ◽  
Vol 90 (22) ◽  
pp. 10362-10378 ◽  
Author(s):  
Matthew R. Costa ◽  
Justin Pollara ◽  
Regina Whitney Edwards ◽  
Michael S. Seaman ◽  
Miroslaw K. Gorny ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Fc Receptor ◽  
Hiv Vaccine ◽  
Small Subset ◽  
Potential Contribution ◽  
Human Monoclonal Antibodies ◽  
Initial Report ◽  
Protein Boost ◽  
Hiv 1

ABSTRACTHIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design.IMPORTANCEThe roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used.

scholarly journals Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrey A. Gorchakov ◽  
Sergey V. Kulemzin ◽  
Sergey V. Guselnikov ◽  
Konstantin O. Baranov ◽  
Tatyana N. Belovezhets ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Viral Escape ◽  
Lung Pathology ◽  
Human Monoclonal Antibodies ◽  
Systematic Analysis ◽  
Treatment And Prevention ◽  
Rational Development ◽  
Small Molecule Drugs

AbstractIn the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC100 below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.

scholarly journals Generation of Neutralizing Human Monoclonal Antibodies against Parvovirus B19 Proteins

1999 ◽  
Vol 73 (3) ◽  
pp. 1974-1979 ◽  
Author(s):  
Andreas Gigler ◽  
Simone Dorsch ◽  
Andrea Hemauer ◽  
Constance Williams ◽  
Sonnie Kim ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Capsid Protein ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Nonstructural Protein ◽  
Parvovirus B19 ◽  
Human Mabs ◽  
Unique Region ◽  
Neutralizing Activity

ABSTRACT Infections caused by human parvovirus B19 are known to be controlled mainly by neutralizing antibodies. To analyze the immune reaction against parvovirus B19 proteins, four cell lines secreting human immunoglobulin G monoclonal antibodies (MAbs) were generated from two healthy donors and one human immunodeficiency virus type 1-seropositive individual with high serum titers against parvovirus. One MAb is specific for nonstructural protein NS1 (MAb 1424), two MAbs are specific for the unique region of minor capsid protein VP1 (MAbs 1418-1 and 1418-16), and one MAb is directed to major capsid protein VP2 (MAb 860-55D). Two MAbs, 1418-1 and 1418-16, which were generated from the same individual have identity in the cDNA sequences encoding the variable domains, with the exception of four base pairs resulting in only one amino acid change in the light chain. The NS1- and VP1-specific MAbs interact with linear epitopes, whereas the recognized epitope in VP2 is conformational. The MAbs specific for the structural proteins display strong virus-neutralizing activity. The VP1- and VP2-specific MAbs have the capacity to neutralize 50% of infectious parvovirus B19 in vitro at 0.08 and 0.73 μg/ml, respectively, demonstrating the importance of such antibodies in the clearance of B19 viremia. The NS1-specific MAb mediated weak neutralizing activity and required 47.7 μg/ml for 50% neutralization. The human MAbs with potent neutralizing activity could be used for immunotherapy of chronically B19 virus-infected individuals and acutely infected pregnant women. Furthermore, the knowledge gained regarding epitopes which induce strongly neutralizing antibodies may be important for vaccine development.

scholarly journals Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma

2020 ◽  
Author(s):  
Nitesh Mishra ◽  
Sanjeev Kumar ◽  
Swarandeep Singh ◽  
Tanu Bansal ◽  
Nishkarsh Jain ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Cross Reactivity ◽  
Type I ◽  
Human Monoclonal Antibodies ◽  
Critical Feature ◽  
Cd4 Binding Site ◽  
Unique Nature ◽  
Hiv 1

AbstractCross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.ImportanceIn the current ongoing COVID-19 pandemic, neutralizing antibodies have been shown to be a critical feature of recovered patients. HIV-1 bnAbs recognize extensively diverse cross-reactive epitopes and tolerate diversity within their core epitope. Given the unique nature of HIV-1 bnAbs and their ability to recognize and/or accommodate viral glycans, we reasoned that the glycan shield of SARS-CoV-2 spike protein can be targeted by HIV-1 specific bnAbs. Herein, we showed that HIV-1 specific antibodies cross-react and neutralize SARS-CoV-2. Understanding cross-reactive neutralization epitopes of antibodies generated in divergent viral infections will provide key evidence for engineering so called super-antibodies (antibodies that can potently neutralize diverse pathogens with similar antigenic features). Such cross-reactive antibodies can provide a blueprint upon which synthetic variants can be generated in the face of future pandemics.

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