Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant
Venkata Viswanadh EdaraCarson NorwoodKatharine FloydLilin LaiMeredith E. Davis-GardnerWilliam Henry HudsonGrace MantusLindsay E. NyhoffMax W. AdelmanRebecca FinemanShivan PatelRebecca ByramDumingu Nipuni GomesMichael GarettHayatu AbdullahiNour BeydounBernadine PanganibanNina McNairKieffer HellmeisterJamila PittsJoy WintersJennifer KleinhenzJacob UsherJames B. O’KeefeAnne PiantadosiJesse J. WaggonerAhmed BabikerDavid S. StephensEvan J. AndersonSrilatha EdupugantiNadine RouphaelRafi AhmedJens WrammertMehul S. Suthar
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Keywords:
spike protein
Polyclonal antibodies
Antibody titer
Virus quantification
Plaque-forming unit
HSL and HSV
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Abstract While there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.
Convalescent plasma
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Convalescent plasma
spike protein
Lineage (genetic)
Coronavirus
2019-20 coronavirus outbreak
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Abstract We tested human sera from large, demographically balanced cohorts of BNT162b2 vaccine recipients (n=51) and COVID-19 patients (n=44) for neutralizing antibodies against SARS-CoV-2 variants B.1.1.7 and B.1.351. Although the effect is more pronounced in the vaccine cohort, both B.1.1.7 and B.1.351 show significantly reduced levels of neutralization by vaccinated and convalescent sera. Age is negatively correlated with neutralization in vaccinee, and levels of variant-specific RBD antibodies are proportional to neutralizing activities.
2019-20 coronavirus outbreak
Antibody response
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Studies of neutralizing antibodies in HIV-1 infected individuals provide insights into the quality of the response that should be possible to elicit with vaccines and ways to design effective immunogens. Some individuals make high titres of exceptional broadly reactive neutralizing antibodies that are of particular interest; however, more modest responses may be a reasonable goal for vaccines. We performed a large cross-sectional study to determine the spectrum of neutralization potency and breadth that is seen during chronic HIV-1 infection.Neutralization potency and breadth were assessed with genetically and geographically diverse panels of 205 chronic HIV-1 sera and 219 Env-pseudotyped viruses representing all major genetic subtypes of HIV-1.Neutralization was measured by using Tat-regulated luciferase reporter gene expression in TZM-bl cells. Serum-neutralizing activity was compared with a diverse set of human mAbs that are widely considered to be broadly neutralizing.We observed a uniform continuum of responses, with most sera displaying some level of cross-neutralization, and approximately 50% of sera neutralizing more than 50% of viruses. Titres of neutralization (potency) were highly correlated with breadth. Many sera had breadth comparable to several of the less potent broadly neutralizing human mAbs.These results help clarify the spectrum of serum-neutralizing activity induced by HIV-1 infection and that should be possible to elicit with vaccines. Importantly, most people appear capable of making low to moderate titres of broadly neutralizing antibodies. Additional studies of these relatively common responses might provide insights for practical and feasible vaccine designs.
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Infectivity
Antibody titer
Coxsackievirus
Cytopathic effect
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Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.
Antibody titer
Coronavirus
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Summary The 7 S and 19 S rabbit antibodies to herpes simplex virus (HSV) from early and late (hyperimmune) sera differed in their ability to sensitize virus for subsequent neutralization by either complement (C′) or anti-γ-globulin (GAR). The early 7 S and 19 S antibodies showed low to negligible neutralizing activity in the absence of C′ or GAR. When C′ was added, however, both of these antibodies showed enhanced neutralizing activity. The early 7 S but not the early 19 S antibody was also capable of sensitizing virus for subsequent neutralization by GAR. The late 19 S antibody could neutralize virus in the absence of C′ or GAR, but its activity was enhanced in the presence of C′ or GAR. The late 7 S antibody showed high neutralizing activity in the absence of C′ or GAR. In the presence of C′, the neutralization rate constants (K) but not the neutralization titers of the late 7 S antibody were enhanced. In contrast, the neutralization titers of the late 7 S antibody were enhanced approximately threefold with GAR. The neutralizing activity of the early and late 19 S antibodies with C′ or GAR was sensitive to inactivation by 2-ME. Similarly, the neutralizing activity with C′ of the early 7 S antibody and the enhanced rate of neutralization with C′ of the late 7 S antibody were sensitive to inactivation by 2-ME. In contrast, 2-ME did not reduce the neutralization titers of the early and late 7 S antibodies in the presence of GAR.
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