scholarly journals The potential of COVID-19 patients’ sera to cause antibody-dependent enhancement of infection and IL-6 production

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Shimizu ◽  
Tadahiro Sasaki ◽  
Atsushi Yamanaka ◽  
Yoko Ichihara ◽  
Ritsuko Koketsu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Vaccine Development ◽  
Myeloid Cell ◽  
Neutralizing Antibody ◽  
Host Cells ◽  
Virus Infections ◽  
Ips Cell ◽  
Antibody Dependent Enhancement ◽  
Vaccine Trials ◽  
Established Cell

AbstractSince the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many vaccine trials have been initiated. An important goal of vaccination is the development of neutralizing antibody (Ab) against SARS-CoV-2. However, the possible induction of antibody-dependent enhancement (ADE) of infection, which is known for other coronaviruses and dengue virus infections, is a particular concern in vaccine development. Here, we demonstrated that human iPS cell-derived, immortalized, and ACE2- and TMPRSS2-expressing myeloid cell lines are useful as host cells for SARS-CoV-2 infection. The established cell lines were cloned and screened based on their function in terms of susceptibility to SARS-CoV-2-infection or IL-6 productivity. Using the resulting K-ML2 (AT) clone 35 for SARS-CoV-2-infection or its subclone 35–40 for IL-6 productivity, it was possible to evaluate the potential of sera from severe COVID-19 patients to cause ADE and to stimulate IL-6 production upon infection with SARS-CoV-2.

scholarly journals Human Immunodeficiency Virus Env-Independent Infection of Human CD4− Cells

2000 ◽  
Vol 74 (23) ◽  
pp. 10994-11000 ◽  
Author(s):  
Shen Pang ◽  
Duan Yu ◽  
Dong Sung An ◽  
Gayle C. Baldwin ◽  
Yiming Xie ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Lines ◽  
Fluorescent Protein ◽  
Vaccine Development ◽  
Alternative Pathway ◽  
Neutralizing Antibody ◽  
Green Fluorescent Protein Gene ◽  
Immunodeficiency Virus ◽  
Green Fluorescent ◽  
Hiv 1

ABSTRACT CD4− epithelial cells covering mucosal surfaces serve as the primary barrier to prevent human immunodeficiency virus type 1 (HIV-1) infection. We used HIV-1 vectors carrying the enhanced green fluorescent protein gene as a reporter gene to demonstrate that HIV-1 can infect some CD4− human epithelial cell lines with low but significant efficiencies. Importantly, HIV-1 infection of these cell lines is independent of HIV-1 envelope proteins. The Env-independent infection of CD4− cells by HIV-1 suggests an alternative pathway for HIV-1 transmission. Even on virions bearing Env, a neutralizing antibody directed against gp120 is incapable of neutralizing the infection of these cells, thus raising potential implications for HIV-1 vaccine development.

scholarly journals Antibody Response against SARS-CoV-2 and Seasonal Coronaviruses in Nonhospitalized COVID-19 Patients

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Natalia Ruetalo ◽  
Ramona Businger ◽  
Karina Althaus ◽  
Simon Fink ◽  
Felix Ruoff ◽  
...  
Keyword(s):  
Antibody Response ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Cross Protection ◽  
Antibody Dependent Enhancement ◽  
Strong Interest

There is strong interest in the nature of the neutralizing antibody response against SARS-CoV-2 in infected individuals. For vaccine development, it is especially important which antibodies confer protection against SARS-CoV-2, if there is a phenomenon called antibody-dependent enhancement (ADE) of infection, and if there is cross-protection by antibodies directed against seasonal coronaviruses.

Immunotherapy against Metastatic Melanoma with Human iPS Cell–Derived Myeloid Cell Lines Producing Type I Interferons

2015 ◽  
Vol 4 (3) ◽  
pp. 248-258 ◽  
Author(s):  
Azusa Miyashita ◽  
Satoshi Fukushima ◽  
Satoshi Nakahara ◽  
Yosuke Kubo ◽  
Aki Tokuzumi ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Cell Lines ◽  
Myeloid Cell ◽  
Type I Interferons ◽  
Type I ◽  
Ips Cell

scholarly journals TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells

Gene Therapy ◽  
2012 ◽  
Vol 20 (5) ◽  
pp. 504-513 ◽  
Author(s):  
M Haruta ◽  
Y Tomita ◽  
A Yuno ◽  
K Matsumura ◽  
T Ikeda ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Lines ◽  
Myeloid Cell ◽  
Antigen Presenting Cells ◽  
Ips Cell ◽  
Cell Source ◽  
Antigen Presenting

scholarly journals In vitro measurements of protein–protein interactions show that antibody affinity governs the inhibition of SARS-CoV-2 spike/ACE2 binding in convalescent serum

2020 ◽  
Author(s):  
Sebastian Fiedler ◽  
Monika A. Piziorska ◽  
Viola Denninger ◽  
Alexey S. Morgunov ◽  
Alison Ilsley ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Vaccine Development ◽  
Serum Antibody ◽  
Neutralizing Antibody ◽  
Binding Energies ◽  
Host Cells ◽  
Spike Protein ◽  
Antibody Affinity ◽  
Plasma Therapy

AbstractThe humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen. By using microfluidic antibody-affinity profiling, we were able to quantify the serum-antibody mediated inhibition of ACE2–spike binding in two SARS-CoV-2 seropositive individuals. Measurements to determine the affinity, concentration, and neutralization potential of antibodies were performed directly in human serum. Using this approach, we demonstrate that the level of inhibition in both samples can be quantitatively described using the binding energies of the binary interactions between the ACE2 receptor and the spike protein, and the spike protein and the neutralizing antibody. These experiments represent a new type of in-solution receptor binding competition assay, which has further potential areas of application ranging from decisions on donor selection for convalescent plasma therapy, to identification of lead candidates in therapeutic antibody development, and vaccine development.

scholarly journals 539 Immunotherapy against metastatic melanoma with iPS cell-derived myeloid cell lines producing IFN-β or IL-15

2017 ◽  
Vol 137 (10) ◽  
pp. S284
Author(s):  
Y. Kubo ◽  
S. Fukushima ◽  
S. Nakahara ◽  
A. Miyashita ◽  
R. Zhang ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Cell Lines ◽  
Myeloid Cell ◽  
Ips Cell

scholarly journals A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 64 ◽  
Author(s):  
Fangfang Wu ◽  
Shengnan Zhang ◽  
Ying Zhang ◽  
Ruo Mo ◽  
Feihu Yan ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Recombinant Baculovirus ◽  
Neutralizing Antibody ◽  
Therapeutic Drug ◽  
Therapeutic Effects ◽  
Structural Protein ◽  
Virus Infections ◽  
Experimental Drugs

Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research.

scholarly journals Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay

2020 ◽  
Author(s):  
E. Taylor Stone ◽  
Elizabeth Geerling ◽  
Tara L. Steffen ◽  
Mariah Hassert ◽  
Alexandria Dickson ◽  
...  
Keyword(s):  
Cell Lines ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Focus Reduction ◽  
Immortalized Cell ◽  
Kinetics Of ◽  
Human Primate

AbstractThe SARS-CoV-2 outbreak and subsequent COVID-19 pandemic have highlighted the urgent need to determine what cells are susceptible to infection and for assays to detect and quantify SARS-CoV-2. Furthermore, the ongoing efforts for vaccine development have necessitated the development of rapid, high-throughput methods of quantifying infectious SARS-CoV-2, as well as the ability to screen human polyclonal sera samples for neutralizing antibodies against SARS-CoV-2. To this end, our lab has adapted focus forming assays for SARS-CoV-2 using Vero CCL-81 cells, referred to in this text as Vero WHO. Using the focus forming assay as the basis for screening cell susceptibility and to develop a focus reduction neutralization test. We have shown that this assay is a sensitive tool for determining SARS-CoV-2 neutralizing antibody titer in human, non-human primate, and mouse polyclonal sera following SARS-CoV-2 exposure. Additionally, we describe the viral growth kinetics of SARS-CoV-2 in a variety of different immortalized cell lines and demonstrate via human ACE2 and viral spike protein expression that these cell lines can support viral entry and replication.

Carbohydrate-Binding Agents: Potential of Repurposing for COVID-19 Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 1085-1096 ◽  
Author(s):  
Rajesh Kumar Gupta ◽  
Girish R. Apte ◽  
Kiran Bharat Lokhande ◽  
Satyendra Mishra ◽  
Jayanta K. Pal
Keyword(s):  
Vaccine Development ◽  
Host Cells ◽  
Carbohydrate Binding ◽  
Atypical Pneumonia ◽  
The Novel ◽  
High Infection ◽  
Binding Agents ◽  
Current Scenario ◽  
Antiviral Activities ◽  
Novel Drug

: With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV- 2, in particular.

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