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

2020 ◽  
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.

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

Immunotherapy ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 1247-1255 ◽  
Author(s):  
José María Díez ◽  
Carolina Romero ◽  
Júlia Vergara-Alert ◽  
Melissa Belló-Perez ◽  
Jordi Rodon ◽  
...  
Keyword(s):  
Cell Culture ◽  
Intravenous Immunoglobulins ◽  
Cross Reactivity ◽  
Percent Reduction ◽  
Neutralization Activity ◽  
Neutralization Capacity ◽  
Ivig Preparation ◽  
Cross Neutralization ◽  
Human Coronaviruses

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.

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

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.

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

Proceedings ◽  
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.

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

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.

scholarly journals Delayed neutralizing antibody response in the acute phase correlates with severe progression of COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hitoshi Kawasuji ◽  
Yoshitomo Morinaga ◽  
Hideki Tani ◽  
Miyuki Kimura ◽  
Hiroshi Yamada ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Pseudotyped Virus ◽  
Serum Samples ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Time Points ◽  
Moderate Disease ◽  
Activity Dynamics

AbstractAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

scholarly journals Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 209 ◽  
Author(s):  
Wilson Nguyen ◽  
Eri Nakayama ◽  
Kexin Yan ◽  
Bing Tang ◽  
Thuy T. Le ◽  
...  
Keyword(s):  
Semliki Forest Virus ◽  
Cross Reactivity ◽  
Cross Protection ◽  
Effective Vaccine ◽  
Protective Capacity ◽  
Heterologous Virus ◽  
Antigenic Complex ◽  
Cross Neutralization ◽  
Mayaro Virus ◽  
Formalin Fixed

Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1-/- mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers.

scholarly journals Validation of Selected Commercial Serological Assays for Diagnosis of COVID-19

2020 ◽  
Author(s):  
Salma Younes ◽  
Hadeel Al-Jighefee ◽  
Farah Shurrab ◽  
Duaa Al-Sadeq ◽  
Hadi Yassine ◽  
...  
Keyword(s):  
Neutralization Test ◽  
Cross Reactivity ◽  
Clinical Settings ◽  
Igg Antibodies ◽  
Excellent Correlation ◽  
Rt Pcr ◽  
Rapid Assays ◽  
Igm Elisa ◽  
Rapid Tests ◽  
Antibody Tests

As researchers around the globe rush to put the available antibody tests to use, concerns have been raised about their precision. This study aimed to evaluate and compare the performance of selected commercial & automated serological assays that are widely used in different clinical settings in Qatar. We validated the performance of five commercial IgG and IgM ELISA kits, three fully automated immunoassays, and two commercial rapid tests. The sensitivity of all assays was compared to RT-PCR and a surrogate virus neutralization test (sVNT). In addition, cross-reactivity was investigated. Among the evaluated kits, Lionex IgG assay demonstrated the best performance (~88% sensitivity and ~99 specificity). All automated assays showed an excellent correlation with the neutralization test with an overall agreement of 93.6-98.5%. The rapid assays demonstrated a very good performance in detecting IgG antibodies (86.0-88.0% sensitivity and 98.0-100% specificity).

scholarly journals A rapid and efficient screening system for neutralizing antibodies and its application for the discovery of potent neutralizing antibodies to SARS-CoV-2 S-RBD

2020 ◽  
Author(s):  
Xiaojian Han ◽  
Yingming Wang ◽  
Shenglong Li ◽  
Chao Hu ◽  
Tingting Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Inhibitory Concentration ◽  
Emerging Infectious Diseases ◽  
Receptor Binding Domain ◽  
Screening System ◽  
High Potency ◽  
Preliminary Screening ◽  
Neutralization Activity ◽  
Prevention And Treatment ◽  
Efficient Screening

AbstractNeutralizing antibodies (Abs) have been considered as promising therapeutics for the prevention and treatment of pathogens. After the outbreak of COVID-19, potent neutralizing Abs to SARS-CoV-2 were promptly developed, and a few of those neutralizing Abs are being tested in clinical studies. However, there were few methodologies detailly reported on how to rapidly and efficiently generate neutralizing Abs of interest. Here, we present a strategically optimized method for precisive screening of neutralizing monoclonal antibodies (mAbs), which enabled us to identify SARS-CoV-2 receptor-binding domain (RBD) specific Abs within 4 days, followed by another 2 days for neutralization activity evaluation. By applying the screening system, we obtained 198 Abs against the RBD of SARS-CoV-2. Excitingly, we found that approximately 50% (96/198) of them were candidate neutralizing Abs in a preliminary screening of SARS-CoV-2 pseudovirus and 20 of these 96 neutralizing Abs were confirmed with high potency. Furthermore, 2 mAbs with the highest neutralizing potency were identified to block authentic SARS-CoV-2 with the half-maximal inhibitory concentration (IC50) at concentrations of 9.88 ng/ml and 11.13 ng/ml. In this report, we demonstrated that the optimized neutralizing Abs screening system is useful for the rapid and efficient discovery of potent neutralizing Abs against SARS-CoV-2. Our study provides a methodology for the generation of preventive and therapeutic antibody drugs for emerging infectious diseases.

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