scholarly journals A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Sisi Shan ◽  
Chee Keng Mok ◽  
Shuyuan Zhang ◽  
Jun Lan ◽  
Jizhou Li ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Human Antibody ◽  
Lung Pathology ◽  
Receptor Binding Domain ◽  
Isolation And Characterization ◽  
Normal Body Weight ◽  
Conserved Epitope

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations—K417N, E484K, and N501Y—found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.

scholarly journals Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuang Wang ◽  
Yun Peng ◽  
Rongjuan Wang ◽  
Shasha Jiao ◽  
Min Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Single Dose ◽  
Rhesus Monkeys ◽  
Prophylactic Treatment ◽  
Neutralizing Antibody ◽  
Therapeutic Effects ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

AbstractEfficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19.

scholarly journals A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice

2021 ◽  
Author(s):  
David R. Martinez ◽  
Alexandra Schaefer ◽  
Sophie Gobeil ◽  
Dapeng Li ◽  
Gabriela De la Cruz ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Receptor Binding ◽  
Specific Antibody ◽  
Neutralizing Antibody ◽  
Affinity Binding ◽  
Receptor Binding Domain ◽  
High Affinity Binding ◽  
High Affinity ◽  
Broadly Neutralizing Antibody ◽  
Conserved Epitope

AbstractSARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

scholarly journals CHARACTERIZATION OF A FACTOR FORMED IN THE COURSE OF ADENOVIRUS INFECTION OF TISSUE CULTURES CAUSING DETACHMENT OF CELLS FROM GLASS

1958 ◽  
Vol 108 (5) ◽  
pp. 713-729 ◽  
Author(s):  
Wallace P. Rowe ◽  
Janet W. Hartley ◽  
Bernard Roizman ◽  
Hilton B. Levy
Keyword(s):  
Tissue Culture ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Cell Detachment ◽  
Tissue Cultures ◽  
Kb Cells ◽  
Temperature Dependent ◽  
Reproducible Method ◽  
Glass Surfaces

Infectious tissue culture fluids of the majority of serotypes of adenovirus at low dilutions detach HeLa or KB cells from glass surfaces within a few hours after inoculation. A reproducible method for testing cell detachment was devised. The factor present in infectious tissue culture fluids and responsible for cell detachment is trypsin-sensitive and non-dialyzable; it is smaller and more resistant to the effect of heat or ultraviolet light than the infectious virus particle. Cell detachment activity was found to be temperature-dependent, and the cell-detaching titer of infectious tissue culture fluids was not affected by repeated exposure to HeLa cells. Inhibition of cell detachment by human or rabbit sera was observed only when other antibodies to adenovirus antigens were also present, but the antibody inhibiting cell detachment could not be correlated quantitatively with complement-fixing or homologous neutralizing antibody.

scholarly journals Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Kuan-Ying A Huang ◽  
Yhu-Chering Huang ◽  
Cheng-Hsun Chiu ◽  
Kuo-Chien Tsao ◽  
Tzou-Yien Lin
Keyword(s):  
Age Groups ◽  
Antigenic Site ◽  
Neutralizing Antibody ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Human Antibody ◽  
Antigenic Characterization ◽  
Before And After ◽  
Viral Emergence

Abstract Background Clade 6B H1N1 pdm09 influenza viruses cause substantial morbidity and mortality worldwide. Human antibody profiles elicited upon vaccination against the clade 6B virus are largely unclear before viral emergence. Methods Healthy volunteers, including children aged 3–8 years, adolescents aged 9–17 years, and adults, were enrolled before the clade 6B H1N1 outbreak and received the 2013–2014 inactivated influenza vaccine. We determined antibody responses before and after vaccination. Vaccine-induced plasmablast-derived antibodies were tested against H1N1 pdm09 reference and clade 6B viruses. Results The majority of the subjects generated robust hemagglutination inhibition and neutralizing antibody responses upon vaccination across the different age groups. Nevertheless, a subset of young adults preferentially produced antibodies that failed to neutralize clade 6B viruses that emerged and circulated in 2014–2016. The hemagglutinin K163Q change at the Sa antigenic site, one of the substitutions that define clade 6B viruses, was responsible for resistance to neutralization by both postvaccination sera and vaccine-induced plasmablast-derived antibodies. Conclusions Vaccine-induced antibody immunity is compromised by the antigenic change of H1N1 pdm09 virus in a subset of adults, and this may warrant the incorporation of human serology in the antigenic characterization of virus and vaccine strain selection.

Isolation and characterization of a human antibody fragment specific for Ts1 toxin from Tityus serrulatus scorpion

2011 ◽  
Vol 139 (1-2) ◽  
pp. 73-79 ◽  
Author(s):  
Itzel Amaro ◽  
Lidia Riaño-Umbarila ◽  
Baltazar Becerril ◽  
Lourival D. Possani
Keyword(s):  
Antibody Fragment ◽  
Human Antibody ◽  
Isolation And Characterization ◽  
Tityus Serrulatus

scholarly journals Isolation and Characterization of Seneca Valley Virus Spread from Pig to Mink

2021 ◽  
Author(s):  
Chao Chen ◽  
Zida Nai ◽  
Yao Wang ◽  
Ziliang Qin ◽  
Qinjian Niu ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Mammalian Host ◽  
Molecular Characteristics ◽  
Virus Spread ◽  
Intestinal Infection ◽  
Response Data ◽  
Systemic Analysis ◽  
Isolation And Characterization ◽  
Seneca Valley Virus

Seneca Valley Virus (SVV) infection has recently spread to pig farms in Canada, America, and China. Humans, mice, and houseflies have been identified as hosts and reservoirs. Although such cross-species transmission events are often limited, sustained outbreaks in a new mammalian host can occur. To determine if mink are a new mammalian host of SSV, we studied the molecular characteristics of isolated SVV genomes and analyzed challenge, pathology, and immune response data. The study was the first systemic analysis of a newly isolated strain of SVV from pigs. The strain caused an intestinal infection with associated pathologic changes in mink. SVV stimulated the production of a specific neutralizing antibody. The findings highlight the importance of identifying SVV infection in mink and the host to detect mutated SSV that could threaten livestock and pose public health and economic risks.

scholarly journals Tiger team: a panel of human neutralizing mAbs targeting SARS-CoV-2 spike at multiple epitopes

2020 ◽  
Author(s):  
Tal Noy-Porat ◽  
Efi Makdasi ◽  
Ron Alcalay ◽  
Adva Mechaly ◽  
Yinon Levy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Phage Display Library ◽  
Therapeutic Drug ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Human Coronavirus ◽  
Isolation And Characterization ◽  
Emerging Virus

AbstractThe novel highly transmissible human coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Thus far, there is no approved therapeutic drug, specifically targeting this emerging virus. Here we report the isolation and characterization of a panel of human neutralizing monoclonal antibodies targeting the SARS-CoV-2 receptor binding domain (RBD). These antibodies were selected from a phage display library constructed using peripheral circulatory lymphocytes collected from patients at the acute phase of the disease. These neutralizing antibodies are shown to recognize distinct epitopes on the viral spike RBD, therefore they represent a promising basis for the design of efficient combined post-exposure therapy for SARS-CoV-2 infection.

scholarly journals An HIV-1 Broadly Neutralizing Antibody from a Clade C-Infected Pediatric Elite Neutralizer Potently Neutralizes the Contemporaneous and Autologous Evolving Viruses

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Sanjeev Kumar ◽  
Harekrushna Panda ◽  
Muzamil Ashraf Makhdoomi ◽  
Nitesh Mishra ◽  
Haaris Ahsan Safdari ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Structural Information ◽  
Neutralizing Antibody ◽  
Elite Controller ◽  
Effective Vaccine ◽  
Protective Effects ◽  
Isolation And Characterization ◽  
Clade C ◽  
Hiv 1

ABSTRACT Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite neutralizers are potential candidates for isolation of HIV-1 bNAbs. The coexistence of bNAbs such as BG18 with neutralization-susceptible autologous viruses in an HIV-1-infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1-infected children than in adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults. Therefore, we evaluated the specificity of plasma neutralizing antibodies of an antiretroviral-naive HIV-1 clade C chronically infected pediatric elite neutralizer, AIIMS_330. The plasma antibodies showed broad and potent HIV-1 neutralizing activity with >87% (29/33) breadth, a median inhibitory dilution (ID50) value of 1,246, and presence of N160 and N332 supersite-dependent HIV-1 bNAbs. The sorting of BG505.SOSIP.664.C2 T332N gp140 HIV-1 antigen-specific single B cells of AIIMS_330 resulted in the isolation of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01. The AIIMS-P01 neutralized 67% of HIV-1 cross-clade viruses, exhibited substantial indels despite limited somatic hypermutations, interacted with native-like HIV-1 trimer as observed in negative stain electron microscopy, and demonstrated high binding affinity. In addition, AIIMS-P01 neutralized the coexisting and evolving autologous viruses, suggesting the coexistence of vulnerable autologous viruses and HIV-1 bNAbs in the AIIMS_330 pediatric elite neutralizer. Such pediatric elite neutralizers can serve as potential candidates for isolation of novel HIV-1 pediatric bNAbs and for understanding the coevolution of virus and host immune response. IMPORTANCE More than 50% of the HIV-1 infections globally are caused by clade C viruses. To date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are under way to design immunogens that can elicit correlates of protection upon vaccination. Here, we report the isolation and characterization of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01, from a clade C chronically infected pediatric elite neutralizer. The N332 supersite is an important epitope and is one of the current HIV-1 vaccine targets. AIIMS-P01 potently neutralized the contemporaneous and autologous evolving viruses and exhibited substantial indels despite low somatic hypermutations. Taken together with the information on infant bNAbs, further isolation and characterization of bNAbs contributing to the plasma breadth in HIV-1 chronically infected children may help provide a better understanding of their role in controlling HIV-1 infection.

scholarly journals The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in non-human primates

2021 ◽  
pp. eabf1906
Author(s):  
Bryan E. Jones ◽  
Patricia L. Brown-Augsburger ◽  
Kizzmekia S. Corbett ◽  
Kathryn Westendorf ◽  
Julian Davies ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Functional Characterization ◽  
Neutralizing Antibody ◽  
Therapeutic Agents ◽  
Receptor Binding Domain ◽  
Angiotensin Converting Enzyme 2 ◽  
Cynomolgus Monkeys ◽  
Binding Inhibition ◽  
Vaccination Campaigns

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics which may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days, and clearance of 0.22 mL/hr/kg, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study Day 6 following viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.

Sign in / Sign up

Export Citation Format

Share Document