Search

Your search keyword '"Oguntuyo, Kasopefoluwa"' showing total 5 results
Start Over "Oguntuyo, Kasopefoluwa" Topic covid-19 Language english
5 results on '"Oguntuyo, Kasopefoluwa"'

1. Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 Sera

Author

Oguntuyo, Kasopefoluwa, Stevens, Christian S., Hung, Chuan Tien, Ikegame, Satoshi, Acklin, Joshua A., Kowdle, Shreyas S., Carmichael, Jillian C., Chiu, Hsin Ping, Azarm, Kristopher D., Haas, Griffin D., Amanat, Fatima, Klingler, Jéromine, Baine, Ian, Arinsburg, Suzanne, Bandres, Juan C., Siddiquey, Mohammed N. A., Schilke, Robert M., Woolard, Matthew D., Zhang, Hongbo, Duty, Andrew J., Kraus, Thomas A., Moran, Thomas M., Tortorella, Domenico, Lim, Jean K., Gamarnik, Andrea Vanesa, Hioe, Catarina E., Zolla Pazner, Susan, Ivanov, Stanimir S., Kamil, Jeremy, Krammer, Florian, Lee, Benhur, Ojeda, Diego Sebastian, González López Ledesma, María Mora, Costa Navarro, Guadalupe Soledad, Pallarés, H. M., Sanchez, Lautaro Nicolas, Perez, P., Ostrowsk, M., Villordo, S. M., Alvarez, D. E., Caramelo, J. J., Carradori, J., and Yanovsky, M. J.

Subjects
viral neutralization assay, medicine.drug_class, Enzyme-Linked Immunosorbent Assay, SARS-COV-2, Monoclonal antibody, Antibodies, Viral, Microbiology, Virus, Neutralization, Article, NEUTRALIZING ANTIBODIES, purl.org/becyt/ford/1 [https], 03 medical and health sciences, 0302 clinical medicine, Viral entry, Neutralization Tests, Virology, Biosafety level, Potency, Medicine, Humans, neutralizing antibodies, 030212 general & internal medicine, purl.org/becyt/ford/1.6 [https], Neutralizing antibody, 030304 developmental biology, convalescent-phase plasma, 0303 health sciences, biology, business.industry, SARS-CoV-2, fungi, COVID-19, VIRAL NEUTRALIZATION ASSAY, Gold standard (test), biology.organism_classification, Antibodies, Neutralizing, QR1-502, body regions, Titer, Vesicular stomatitis virus, biology.protein, Antibody, business, CONVALESCENT-PHASE PLASMA, Research Article
Abstract

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glyco-protein (VSVDG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n . 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week. IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We there-fore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy. Fil: Oguntuyo, Kasopefoluwa. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Stevens, Christian S.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Hung, Chuan Tien. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Ikegame, Satoshi. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Acklin, Joshua A.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Kowdle, Shreyas S.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Carmichael, Jillian C.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Chiu, Hsin Ping. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Azarm, Kristopher D.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Haas, Griffin D.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Amanat, Fatima. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Klingler, Jéromine. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Baine, Ian. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Arinsburg, Suzanne. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Bandres, Juan C.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Siddiquey, Mohammed N. A.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Schilke, Robert M.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Woolard, Matthew D.. State University of Louisiana; Estados Unidos Fil: Zhang, Hongbo. State University of Louisiana; Estados Unidos Fil: Duty, Andrew J.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Kraus, Thomas A.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Moran, Thomas M.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Tortorella, Domenico. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Lim, Jean K.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Hioe, Catarina E.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Zolla Pazner, Susan. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Ivanov, Stanimir S.. State University of Louisiana; Estados Unidos Fil: Kamil, Jeremy. State University of Louisiana; Estados Unidos Fil: Krammer, Florian. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Lee, Benhur. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: González López Ledesma, María Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Costa Navarro, Guadalupe Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Pallarés, H. M.. No especifíca; Fil: Sanchez, Lautaro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Perez, P.. No especifíca; Fil: Ostrowsk, M.. No especifíca; Fil: Villordo, S. M.. No especifíca; Fil: Alvarez, D. E.. No especifíca; Fil: Caramelo, J. J.. No especifíca; Fil: Carradori, J.. No especifíca; Fil: Yanovsky, M. J.. No especifíca

Published
2021
Full Text
View/download PDF

2. SARS-CoV-2 mRNA vaccines induce a greater array of spike-specific antibody isotypes with more potent complement binding capacity than natural infection

Author

Klingler, Jéromine, Lambert, Gregory S., Itri, Vincenza, Liu, Sean, Bandres, Juan C., Enyindah-Asonye, Gospel, Liu, Xiaomei, Oguntuyo, Kasopefoluwa Y., Amanat, Fatima, Lee, Benhur, Zolla-Pazner, Susan, Upadhyay, Chitra, and Hioe, Catarina E.

Subjects
Adult, Male, saliva, COVID-19 Vaccines, SARS-CoV-2, Vaccination, COVID-19, ADCP, neutralization, Middle Aged, Antibodies, Viral, Antibodies, Neutralizing, Article, antibody isotypes, Immunoglobulin G, Antibody Formation, Spike Glycoprotein, Coronavirus, Humans, Female, complement fixation, Aged
Abstract

Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.

Published
2021

3. Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants.

Author

Ikegame, Satoshi, Siddiquey, Mohammed N. A., Hung, Chuan-Tien, Haas, Griffin, Brambilla, Luca, Oguntuyo, Kasopefoluwa Y., Kowdle, Shreyas, Chiu, Hsin-Ping, Stevens, Christian S., Vilardo, Ariel Esteban, Edelstein, Alexis, Perandones, Claudia, Kamil, Jeremy P., and Lee, Benhur

Subjects
SARS-CoV-2, COVID-19 vaccines, IMMUNOGLOBULINS, COVID-19 pandemic, VESICULAR stomatitis, COVID-19
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 180 million people since its identification as the cause of the current COVID-19 pandemic. The rapid pace of vaccine development has resulted in multiple vaccines already in use worldwide. The contemporaneous emergence of SARS-CoV-2 'variants of concern' (VOC) across diverse geographic locales underscores the need to monitor the efficacy of vaccines being administered globally. All WHO designated VOC carry spike (S) polymorphisms thought to enable escape from neutralizing antibodies. Here, we characterize the neutralizing activity of post-Sputnik V vaccination sera against the ensemble of S mutations present in alpha (B.1.1.7) and beta (B.1.351) VOC. Using de novo generated replication-competent vesicular stomatitis virus expressing various SARS-CoV-2-S in place of VSV-G (rcVSV-CoV2-S), coupled with a clonal 293T-ACE2 + TMPRSS2 + cell line optimized for highly efficient S-mediated infection, we determine that only 1 out of 12 post-vaccination serum samples shows effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralize S from B.1.1.7 and exhibit only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines. Here, the authors characterize the neutralization capacity of post-Sputnik V vaccination sera against SARS-CoV-2 variants of concern B.1.1.7 (alpha) and B.1.351 (beta), showing the latter to exhibit resistance to neutralization in vitro. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

4. Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2.

Author

Klingler, Jéromine, Weiss, Svenja, Itri, Vincenza, Liu, Xiaomei, Oguntuyo, Kasopefoluwa Y, Stevens, Christian, Ikegame, Satoshi, Hung, Chuan-Tien, Enyindah-Asonye, Gospel, Amanat, Fatima, Baine, Ian, Arinsburg, Suzanne, Bandres, Juan C, Kojic, Erna Milunka, Stoever, Jonathan, Jurczyszak, Denise, Bermudez-Gonzalez, Maria, Nádas, Arthur, Liu, Sean, and Lee, Benhur

Subjects
IMMUNOGLOBULIN M, CONVALESCENT plasma, COVID-19, CORONAVIRUS disease treatment, VESICULAR stomatitis
Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin isotypes capable of blocking infection.Methods: We studied spike- and RBD-specific immunoglobulin isotypes in convalescent and acute plasma/serum samples using a multiplex bead assay. We also determined virus neutralization activities in plasma and serum samples, and purified immunoglobulin fractions using a vesicular stomatitis pseudovirus assay.Results: Spike- and RBD-specific immunoglobulin (Ig) M, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions' neutralization potency. IgA also exhibited neutralizing activity, but with lower potency.Conclusion: IgG, IgM, and IgA are critical components of convalescent plasma used for treatment of coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

5. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection.

Author

Wei, Jin, Alfajaro, Mia Madel, DeWeirdt, Peter C., Hanna, Ruth E., Lu-Culligan, William J., Cai, Wesley L., Strine, Madison S., Zhang, Shang-Min, Graziano, Vincent R., Schmitz, Cameron O., Chen, Jennifer S., Mankowski, Madeleine C., Filler, Renata B., Ravindra, Neal G., Gasque, Victor, de Miguel, Fernando J., Patil, Ajinkya, Chen, Huacui, Oguntuyo, Kasopefoluwa Y., and Abriola, Laura

Subjects
*COVID-19, *SARS-CoV-2, *GENE libraries, *CRISPRS, *VESICULAR stomatitis, *MERS coronavirus
Abstract

Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs. • Developed monkey CRISPR library to screen pathogenic coronaviruses in Vero-E6 cells • Screens identified genes that are SARS-CoV-2, MERS-CoV, and pan-coronavirus specific • Therapeutic targets, including SMARCA4, identified for SARS-CoV-2 infection • HMGB1 is novel regulator of ACE2 expression and critical for viral entry To identify potential therapeutic targets for SARS-CoV-2 and related pathogenic coronaviruses, Wei et al. conduct genome-wide CRISPR screens in Vero-E6 cells using SARS-CoV-2, MERS-CoV, and pseudoviruses presenting SARS-CoV-1 or SARS-CoV-2 spike proteins. They identify pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively, and demonstrate that HMGB1 is critical for SARS lineage viral entry because it has a critical role in ACE2 expression. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results