scholarly journals Limited window for donation of convalescent plasma with high live-virus neutralizing antibodies for COVID-19 immunotherapy

2020 ◽  
Author(s):  
Abhinay Gontu ◽  
Sreenidhi Srinivasan ◽  
Eric Salazar ◽  
Meera Surendran Nair ◽  
Ruth H. Nissly ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Igg Antibody ◽  
Plasma Therapy ◽  
Live Virus ◽  
Viral Neutralization ◽  
Knowledge Deficit ◽  
Neutralizing Capacity ◽  
Optimal Window

ABSTRACTThe optimal timeframe for donating convalescent plasma to be used for COVID-19 immunotherapy is unknown. To address this important knowledge deficit, we determined in vitro live-virus neutralizing capacity and persistence of IgM and IgG antibody responses against the receptor-binding domain and S1 ectodomain of the SARS-CoV-2 spike glycoprotein in 540 convalescent plasma samples obtained from 175 COVID-19 plasma donors for up to 142 days post-symptom onset. Robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 persist, in the aggregate, for at least 100 days post-symptom onset. However, a notable acceleration in decline in virus neutralization titers ≥160, a value suitable for convalescent plasma therapy, was observed starting 60 days after first symptom onset. Together, these findings better define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor, including age and COVID-19 disease severity score.One Sentence SummaryEvaluation of SARS-CoV-2 anti-spike protein IgM, IgG, and live-virus neutralizing titer profiles reveals that the optimal window for donating convalescent plasma for use in immunotherapy is within the first 60 days of symptom onset.

scholarly journals Limited window for donation of convalescent plasma with high live-virus neutralizing antibody titers for COVID-19 immunotherapy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Abhinay Gontu ◽  
Sreenidhi Srinivasan ◽  
Eric Salazar ◽  
Meera Surendran Nair ◽  
Ruth H. Nissly ◽  
...  
Keyword(s):  
Age Groups ◽  
Neutralizing Antibody ◽  
Igg Antibody ◽  
Plasma Therapy ◽  
Live Virus ◽  
Viral Neutralization ◽  
Antibody Titers ◽  
Plasma Donor ◽  
Optimal Window

AbstractMillions of individuals who have recovered from SARS-CoV-2 infection may be eligible to participate in convalescent plasma donor programs, yet the optimal window for donating high neutralizing titer convalescent plasma for COVID-19 immunotherapy remains unknown. Here we studied the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers (VN) in 175 convalescent donors longitudinally sampled for up to 142 days post onset of symptoms (DPO). We observed robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 that persist, in the aggregate, for at least 100 DPO. However, there is a notable decline in VN titers ≥160 for convalescent plasma therapy, starting 60 DPO. The results also show that individuals 30 years of age or younger have significantly lower VN, IgG and IgM antibody titers than those in the older age groups; and individuals with greater disease severity also have significantly higher IgM and IgG antibody titers. Taken together, these findings define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor.

scholarly journals A rapid real-time polymerase chain reaction-based live virus microneutralization assay for detection of neutralizing antibodies against SARS-CoV-2 in blood/serum

2021 ◽  
Author(s):  
Syed Hani Abidi ◽  
Kehkeshan Imtiaz ◽  
Akbar Kanji ◽  
Shama Qaiser ◽  
Erum Khan ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vero Cells ◽  
Neutralization Assay ◽  
Dilution Method ◽  
Rt Pcr ◽  
Serum Samples ◽  
Live Virus ◽  
Viral Neutralization ◽  
Microneutralization Assay ◽  
Infected Cells

Abstract Background Individuals recovering from COVID-19 are shown to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability and some may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 neutralizing assays that allow the determination of virus neutralizing activity in sera of individuals. Here we describe a PCR-based micro-neutralization assay that can be used to evaluate the viral neutralization titers of serum from SARS-CoV-2 infected individuals. Methods The SARS-CoV-2 strain used was isolated from a nasopharyngeal specimen of a COVID-19 case. The limiting dilution method was used to obtain a 50% tissue culture infective dose (TCID50) of Vero cells. For the micro‐neutralization assay, 19 serum samples, with positive IgG titers against Spike receptor binding domain (RBD) were tested. After 24 hours, infected cells were inspected for the presence of the cytopathic effect, then lysed and RNA RT-PCR of SARS-CoV-2. The Ct values were used to calculate percent neutralization/inhibition of SARS-CoV-2. Results Out of 19 samples, 13 samples gave 100% neutralization at all dilutions, while 4 samples gave neutralization at lower dilution, while one sample did not give any neutralization. The correlation between RBD OD and neutralization potential was found to be statistically correlated. Conclusion We describe a rapid RT-PCR based SARS-CoV-2 microneutralization assay for detection of neutralizing antibodies. This can effectively be used to test anti-viral activity of serum antibodies for investigation of both disease-driven and vaccine-induced responses.

scholarly journals Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients

2021 ◽  
Author(s):  
Jira Chansaenroj ◽  
Ritthideach Yorsaeng ◽  
Nasamon Wanlapakorn ◽  
Chintana Chirathaworn ◽  
Natthinee Sudhinaraset ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Immunological Study ◽  
Igg Antibody ◽  
Vaccine Schedule

Abstract Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 in a cohort of patients who were previously infected with SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of SARS-CoV-2 infection were enrolled in our immunological study. The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5 – 327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time depends on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

scholarly journals SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants

2020 ◽  
Author(s):  
Fiona Tea ◽  
Alberto Ospina Stella ◽  
Anupriya Aggarwal ◽  
David Ross Darley ◽  
Deepti Pilli ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Plasma Therapy ◽  
Nucleocapsid Proteins ◽  
Viral Neutralization ◽  
Serial Samples ◽  
High Responders ◽  
Neutralization Response ◽  
Selection Of

AbstractThe SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of ‘high responders’ maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.One Sentence SummaryNeutralizing antibody responses to SARS-CoV-2 are sustained, associated with COVID19 severity, and evaded by emerging viral variants

scholarly journals Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates

2021 ◽  
Author(s):  
Joseph R. Francica ◽  
Barbara J. Flynn ◽  
Kathryn E. Foulds ◽  
Amy T. Noe ◽  
Anne P. Werner ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Viral Infections ◽  
Antibody Responses ◽  
High Dose ◽  
Post Challenge ◽  
Igg Antibody ◽  
Live Virus ◽  
Virus Challenge ◽  
Humoral Responses

AbstractAdjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×106 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials.

scholarly journals A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in rhesus macaques

2021 ◽  
Author(s):  
Ronald R. Cobb ◽  
Joseph Nkolola ◽  
Pavlo Gilchuk ◽  
Abishek Chandrashekar ◽  
Robert V. House ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Post Exposure Prophylaxis ◽  
Human Mabs ◽  
Viral Neutralization ◽  
Exposure Prophylaxis ◽  
Human Primate

Human monoclonal antibody (mAb) treatments are promising for COVID-19 prevention, post-exposure prophylaxis, or therapy. However, the titer of neutralizing antibodies required for protection against SARS-CoV-2 infection remains poorly characterized. We previously described two potently neutralizing mAbs COV2-2130 and COV2-2381 targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein. Here, we engineered the Fc-region of these mAbs with mutations to extend their persistence in humans and reduce interactions with Fc gamma receptors. Passive transfer of individual or combinations of the two antibodies (designated ADM03820) given prophylactically by intravenous or intramuscular route conferred virological protection in a non-human primate (NHP) model of SARS-CoV-2 infection, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro. We defined 6,000 as a protective serum neutralizing antibody titer in NHPs against infection for passively transferred human mAbs that acted by direct viral neutralization, which corresponded to a concentration of 20 microgram/mL of circulating mAb.

scholarly journals Serology in Children with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19

2020 ◽  
Author(s):  
Christina A. Rostad ◽  
Ann Chahroudi ◽  
Grace Mantus ◽  
Stacey A. Lapp ◽  
Mehgan Teherani ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Limit Of Detection ◽  
Geometric Mean ◽  
Neutralization Assay ◽  
Adverse Outcomes ◽  
Igg Antibody ◽  
Live Virus ◽  
Lengths Of Stay ◽  
Antibody Titers ◽  
Inflammatory Syndrome

Objectives: We aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and other hospitalized pediatric controls. Methods: From March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children at Children's Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies by quantitative ELISA and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody titers among groups and performed correlation analyses using linear regression. Results: All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated strongly with neutralizing antibodies (R2=0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010). Conclusion: Quantitative SARS-CoV-2 RBD antibody titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.

scholarly journals A Recombinant Zika Virus Envelope Protein with Mutations in the Conserved Fusion Loop Leads to Reduced Antibody Cross-Reactivity upon Vaccination

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 603
Author(s):  
Beatrice Sarah Berneck ◽  
Alexandra Rockstroh ◽  
Jasmin Fertey ◽  
Thomas Grunwald ◽  
Sebastian Ulbert
Keyword(s):  
Zika Virus ◽  
Insect Cell ◽  
Neutralizing Antibodies ◽  
Structural Similarity ◽  
Cross Reactivity ◽  
Virus Envelope ◽  
E Protein ◽  
Neutralizing Capacity ◽  
Fusion Loop

Zika virus (ZIKV) is a zoonotic, human pathogenic, and mosquito-borne flavivirus. Its distribution is rapidly growing worldwide. Several attempts to develop vaccines for ZIKV are currently ongoing. Central to most vaccination approaches against flavivirus infections is the envelope (E) protein, which is the major target of neutralizing antibodies. Insect-cell derived, recombinantly expressed variants of E from the flaviviruses West Nile and Dengue virus have entered clinical trials in humans. Also for ZIKV, these antigens are promising vaccine candidates. Due to the structural similarity of flaviviruses, cross-reactive antibodies are induced by flavivirus antigens and have been linked to the phenomenon of antibody-dependent enhancement of infection (ADE). Especially the highly conserved fusion loop domain (FL) in the E protein is a target of such cross-reactive antibodies. In areas where different flaviviruses co-circulate and heterologous infections cannot be ruled out, this is of concern. To exclude the possibility that recombinant E proteins of ZIKV might induce ADE in infections with related flaviviruses, we performed an immunization study with an insect-cell derived E protein containing four mutations in and near the FL. Our data show that this mutant antigen elicits antibodies with equal neutralizing capacity as the wildtype equivalent. However, it induces much less serological cross-reactivity and does not cause ADE in vitro. These results indicate that mutated variants of the E protein might lead to ZIKV and other flavivirus vaccines with increased safety profiles.

scholarly journals SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dianna L. Ng ◽  
Gregory M. Goldgof ◽  
Brian R. Shy ◽  
Andrew G. Levine ◽  
Joanna Balcerek ◽  
...  
Keyword(s):  
San Francisco ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Immunoglobulin M ◽  
Bay Area ◽  
Neutralizing Capacity ◽  
Antibody Titers ◽  
Different Populations ◽  
Low Prevalence

Abstract Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.

scholarly journals SARS-CoV-2 variants of concern exhibit reduced sensitivity to live-virus neutralization in sera from CoronaVac vaccinees and naturally infected COVID-19 patients

2021 ◽  
Author(s):  
Vimvara Vacharathit ◽  
Pakorn Aiewsakun ◽  
Suwimon Manopwisedjaroen ◽  
Chanya Srisaowakarn ◽  
Thanida Laopanupong ◽  
...  
Keyword(s):  
Low Income ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Mitigation Strategies ◽  
Low Income Countries ◽  
Live Virus ◽  
Neutralizing Capacity ◽  
Need To Evaluate ◽  
Beijing China ◽  
Spike Sequence

Recent surges in SARS-CoV-2 variants of concern (VOCs) call for the need to evaluate levels of vaccine- and infection- induced SARS-CoV-2 neutralizing antibodies (NAbs). CoronaVac (Sinovac Biotech, Beijing, China) is currently being used for mass vaccination in Thailand as well as other low-income countries. Three VOCs currently circulating within Thailand include the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) strains. We assessed NAb potency against the prototypic strain containing the original spike sequence (WT) compared to that against the 3 VOCs using sera derived from a cohort of healthcare workers who received a full 2-dose regimen of CoronaVac. Sera from two other cohorts consisting of COVID-19 patients who had been hospitalized in 2020 and 2021 were evaluated for comparison. We found that, despite equally robust production of S1-RBD-binding IgG and 100% seropositivity, sera from both CoronaVac vaccinees and naturally infected individuals had significantly reduced neutralizing capacity against all 3 VOCs compared to WT. Strikingly, NAb titers against Alpha and Beta were comparable, but Delta appears to be significantly more refractory to NAbs in all groups. Our results may help inform on CoronaVac NAb-inducing capacity, which is a proxy for vaccine efficacy, in the context of the WT strain and 3 VOCs. Our results also have critical implications for public health decisionmakers who may need to maintain efficient mitigation strategies amid a potentially high risk for infection with VOCs even in those who have been previously infected.

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