Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins

Background: Cross-reactivity against human coronaviruses with Flebogamma® DIF and Gamunex®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.

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Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins

10.1101/2020.06.19.160879 ◽

2020 ◽

Cited By ~ 1

Author(s):

José-María Díez ◽

Carolina Romero ◽

Júlia Vergara-Alert ◽

Melissa Belló-Perez ◽

Jordi Rodon ◽

...

Keyword(s):

Inhibitory Concentration ◽

Neutralization Test ◽

Intravenous Immunoglobulins ◽

Cross Reactivity ◽

Percent Reduction ◽

Neutralization Activity ◽

Neutralization Capacity ◽

Cytopathic Effects ◽

Ivig Preparation ◽

Cross Neutralization

AbstractBackgroundThere is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy.MethodsThe neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10 dilution which reduced the viral titer by 50%).ResultsAll IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50 titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50 ~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50 values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV.ConclusionIn cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management.

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Analysis of Humoral Immune Responses in Chikungunya Virus (CHIKV)-Infected Patients and Individuals Vaccinated With a Candidate CHIKV Vaccine

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz658 ◽

2019 ◽

Vol 221 (10) ◽

pp. 1713-1723

Author(s):

Lisa Henss ◽

Constanze Yue ◽

Christine Von Rhein ◽

Roland Tschismarov ◽

Lia Laura Lewis-Ximenez ◽

...

Keyword(s):

Immune Responses ◽

Chikungunya Virus ◽

Cross Reactivity ◽

Similar Extent ◽

Serum Samples ◽

Neutralization Activity ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Cross Neutralization ◽

Binding Avidity

Abstract Background Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after 1 week, but chronic arthralgia can persist for years. In this study, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed. Methods Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors, and antibody epitope mapping was performed with a peptide array. Results The greatest CHIKV neutralization activity was observed 60–92 days after onset of symptoms. The amount of CHIKV-specific antibodies and their binding avidity and cross-reactivity with other alphaviruses increased over time. Chikungunya virus and o’nyong-nyong virus (ONNV) were both neutralized to a similar extent. Linear antibody binding epitopes were mainly found in E2 domain B and the acid-sensitive regions (ASRs). In addition, serum samples from healthy volunteers vaccinated with a measles-vectored chikungunya vaccine candidate, MV-CHIK, were analyzed. Neutralization activity in the samples from the vaccine cohort was 2- to 6-fold lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination only induced cross-neutralization with ONNV, and the E2 ASR1 was the major antibody target. Conclusions These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.

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Going beyond clinical routine in SARS-CoV-2 antibody testing - A multiplex corona virus antibody test for the evaluation of cross-reactivity to endemic coronavirus antigens

10.1101/2020.07.17.20156000 ◽

2020 ◽

Cited By ~ 3

Author(s):

Matthias Becker ◽

Monika Strengert ◽

Daniel Junker ◽

Tobias Kerrinnes ◽

Philipp D. Kaiser ◽

...

Keyword(s):

Vaccine Development ◽

Antibody Test ◽

Cross Reactivity ◽

Antibody Testing ◽

N Protein ◽

Humoral Immune ◽

In Vitro Diagnostic ◽

Human Coronaviruses ◽

Multiplexed Immunoassay

Given the importance of the humoral immune response to SARS-CoV-2 as a global benchmark for immunity, a detailed analysis is needed to (i) monitor seroconversion in the general population, (ii) understand manifestation and progression of the disease, and (iii) predict the outcome of vaccine development. Currently available serological assays utilize single analyte technologies such as ELISA to measure antibodies against SARS-CoV-2 antigens including spike (S) or nucleocapsid (N) protein. To measure individual antibody (IgG and IgA) responses against SARS-CoV-2 and the endemic human coronaviruses (hCoVs) NL63, 229E, OC43, and HKU1, we developed a multiplexed immunoassay (CoVi-plex), for which we included S and N proteins of these coronaviruses in an expanded antigen panel. Compared to commercial in vitro diagnostic (IVD) tests our CoVi-plex achieved the highest sensitivity and specificity when analyzing 310 SARS-CoV-2 infected and 866 uninfected individuals. Simultaneously we see high IgG responses against hCoVs throughout all samples, whereas no consistent cross reactive IgG response patterns can be defined. In summary, our CoVi-plex is highly suited to monitor vaccination studies and will facilitate epidemiologic screenings for the humoral immunity toward pandemic as well as endemic coronaviruses.

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Analysis of Humoral Immune Responses in Chikungunya Virus (CHIKV)-Infected Patients and Individuals Vaccinated with a Candidate CHIKV Vaccine

Proceedings ◽

10.3390/proceedings2020050095 ◽

2020 ◽

Vol 50 (1) ◽

pp. 95

Author(s):

Lisa Henss ◽

Constanze Yue ◽

Christine von Rhein ◽

Roland Tschismarov ◽

Lia-Laura Lewis-Ximenez ◽

...

Keyword(s):

Immune Responses ◽

Chikungunya Virus ◽

Cross Reactivity ◽

Similar Extent ◽

Serum Samples ◽

Neutralization Activity ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Cross Neutralization ◽

Binding Avidity

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after one week, but chronic arthralgia can persist for years. Here, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed. Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors and antibody epitope mapping was performed with a peptide array. The greatest CHIKV neutralization activity was observed 60–92 days after onset of symptoms. The amount of CHIKV-specific antibodies, their binding avidity, and cross-reactivity with other alphaviruses increased over time. CHIKV and o’nyong-nyong virus (ONNV) were both neutralized to a similar extent. Linear antibody binding epitopes were mainly found in E2 domain B and the acid-sensitive regions (ASRs). In addition, serum samples from healthy volunteers vaccinated with a measles-vectored Chikungunya vaccine candidate, MV-CHIK, were analyzed. Neutralization activity in the samples from the vaccine cohort was lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination induced cross-neutralization with ONNV and the E2 ASR1 was the major antibody target. These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.

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Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals

10.1101/2020.06.12.20129460 ◽

2020 ◽

Author(s):

Jian Zhang ◽

Qian Wu ◽

Ziyan Liu ◽

Qijie Wang ◽

Jiajing Wu ◽

...

Keyword(s):

Vaccine Development ◽

Severe Disease ◽

Neutralizing Antibody ◽

Cross Reactivity ◽

Igg Antibodies ◽

Follicular Cells ◽

Neutralization Activity ◽

Severe Group ◽

Cross Neutralization ◽

Critical Patients

SummarySeroconversion appeared early after COVID-19 onset, and convalescent sera therapy benefit some critical patients. However, neutralizing antibody (nAb) in convalescents is largely unknown. We found that 97.01% (65/67) of COVID-19 convalescents maintained IgG antibodies with high binding and avidity to SARS-CoV-2 spike subunits S1 and S2, and 95.52% (64/67) had neutralization activity against SARS-CoV-2 pesudovirus, one month after discharge (median ID50, 2.75; IQR, 2.34-3.08). Some sera exhibited cross-neutralization against SARS-CoV (76.12%), MERS-CoV (17.91%), or both (10.45%). Interestingly, individuals recovered from severe disease (severe group) had nAbs with binding and neutralization titers higher than non-severe group. Severe group appeared a rapid increase of lymphocytes and a high proportion of circulating CXCR3+ Tfh cells. Interestingly, the later were spike-specific and positively correlated with SARS-CoV-2 nAb titers. All subjects had no autoimmunity. Our findings provide novel insights into nAb responses in COVID-19 convalescents and facilitate treatment and vaccine development for SARS-CoV-2 infection.

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Effective presence of antibodies against common human coronavirus in IgG immunoglobulin medicinal products.

10.1101/2021.07.23.453571 ◽

2021 ◽

Author(s):

José-María Díez ◽

Carolina Romero ◽

Rodrigo Gajardo

Keyword(s):

Specific Activity ◽

Slovak Republic ◽

Geographic Origin ◽

Cross Reactivity ◽

Medicinal Products ◽

Neutralization Activity ◽

Routes Of Administration ◽

Plasma Pool ◽

Level Of Activity ◽

Human Coronaviruses

Introduction: In this series of studies, immunoglobulin products (IgG) formulated for different routes of administration (IV, IM, SC) and prepared from geographically diverse plasma pools were tested for activity against common human coronaviruses (HCoV). IgG products from plasma obtained from Germany, Czech Republic, Slovak Republic, USA and Spain were tested for antibodies to four common HCoV: 229E, OC43, NL63 and HKU1. Since these products are manufactured from pooled plasma from thousands of donors, the antibodies therein are a representation of the HCoV exposure of the population at large. Methods: IgG products of different concentrations manufactured from geographically diverse plasma pools were tested for antibodies to four common HCoV by ELISA. In addition, neutralization assays were conducted using HCoV-229E expressed in MRC5 cells. Complete concentration-neutralization curves were obtained to calculate potencies. Results: The ELISA assays showed that when expressed as specific activity (anti-HCoV activity/mg IgG) similar activity against the four common HCoV was seen across the IgG products regardless of concentration or geographic origin. Highest anti-HCoV activity was seen against HCoV-229E, followed by HCoV-OC43 and then HCoV-NL63 and HCoV-HKU1. The neutralization assays showed similar potency for two preparations of IgG prepared by different processes. Conclusions: These studies are the first demonstration of antibodies to common HCoV in IgG products. The level of activity was similar regardless of the geographic origin of the plasma pool. These antibodies demonstrated neutralization activity against HCoV-229E in MRC5 cells. These results may explain the cross-reactivity seen with pre-pandemic IgG products and SARS-CoV-2 and contribute to the variability in disease course in different patients.

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Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity

Nature Communications ◽

10.1038/s41467-021-20973-3 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Matthias Becker ◽

Monika Strengert ◽

Daniel Junker ◽

Philipp D. Kaiser ◽

Tobias Kerrinnes ◽

...

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Cross Reactivity ◽

Response Patterns ◽

Nucleocapsid Proteins ◽

Humoral Immune ◽

In Vitro Diagnostic ◽

Human Coronaviruses ◽

Sample Set

AbstractThe humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.

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In Vivo and In Vitro Cross Neutralization Studies of Local Rabies Virus Isolates with ERA Based Cell Culture Anti-Rabies Vaccine Produced In Ethiopia

Journal of Vaccines & Vaccination ◽

10.4172/2157-7560.1000256 ◽

2014 ◽

Vol 05 (06) ◽

Author(s):

Abebe Mengesha Aga Yalemtsehay Mekonnen

Keyword(s):

Cell Culture ◽

Rabies Virus ◽

Rabies Vaccine ◽

Cross Neutralization ◽

Virus Isolates

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In Vitro Rapid Antigen Test Performance with the SARS-CoV-2 Variants of Concern B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta)

Microorganisms ◽

10.3390/microorganisms9091967 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1967

Author(s):

Sabrina Jungnick ◽

Bernhard Hobmaier ◽

Lena Mautner ◽

Mona Hoyos ◽

Maren Haase ◽

...

Keyword(s):

Test Performance ◽

Culture Medium ◽

Limit Of Detection ◽

Cross Reactivity ◽

N Protein ◽

Comparable Performance ◽

Other Substances ◽

Antigen Tests ◽

Human Coronaviruses

Rapid antigen tests (RATs) are an integral part of SARS-CoV-2 containment strategies. As emerging variants of concern (VOCs) displace the initially circulating strains, it is crucial that RATs do not fail to detect these new variants. In this study, four RATs for nasal swab testing were investigated using cultured strains of B.1.1 (non-VOC), B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta). Based on dilution series in cell culture medium and pooled saliva, the limit of detection of these RATs was determined in a laboratory setting. Further investigations on cross-reactivity were conducted using recombinant N-protein from seasonal human coronaviruses (hCoVs). RATs evaluated showed an overall comparable performance with cultured strains of the non-VOC B.1.1 and the VOCs Alpha, Beta, Gamma, and Delta. No cross-reactivity was detected with recombinant N-protein of the hCoV strains HKU1, OC43, NL63, and 229E. A continuous evaluation of SARS-CoV-2 RAT performance is required, especially with regard to evolving mutations. Moreover, cross-reactivity and interference with pathogens and other substances on the test performance of RATs should be consistently investigated to ensure suitability in the context of SARS-CoV-2 containment.

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