scholarly journals Spike protein antibodies mediate the apparent correlation between SARS-CoV-2 nucleocapsid antibodies and neutralization test results

2021 ◽  
Author(s):  
Thomas Perkmann ◽  
Thomas Koller ◽  
Nicole Perkmann-Nagele ◽  
Miriam Klausberger ◽  
Mark Duerkop ◽  
...  
Keyword(s):  
Partial Correlation ◽  
Correlation Coefficients ◽  
Spike Protein ◽  
Viral Neutralization ◽  
Mediation Analyses ◽  
Apparent Correlation ◽  
Antibody Assays ◽  
Protein Components ◽  
Antibody Levels ◽  
Viral Nucleocapsid

AbstractObjectivesSARS-CoV-2 infection induces the formation of different antibodies. However, not all of which might prevent the virus from entering the cell, although their concentrations correlate with the titers of viral neutralization tests (NTs). Antibodies against the viral nucleocapsid (NC), e.g., can be classified as such. We aimed to prove the hypothesis that the apparent correlation between NC-antibody levels and NT-titers is mediated by simultaneously occurring antibodies against viral spike-protein components.MethodsWe included 64 individuals with previous SARS-CoV-2 infection (>14d after symptom onset). SARS-CoV-2 antibodies against the NC (Roche total antibody ECLIA, Abbott IgG CMIA) and spike-protein (Technozym RBD ELISA, DiaSorin S1/S2 CLIA) were measured, and neutralization tests were performed. The effect of spike-protein antibodies on the correlation between NC-antibodies and NT-titers was evaluated by partial correlation and mediation analyses.ResultsBoth tested assays assessing antibodies against the NC correlated significantly with NT titers: Abbott ρ=0.742, P<0.0001; Roche ρ=0.365, P<0.01. However, when controlling the rank correlations for the presence of RBD or S1/S2 antibodies, correlation coefficients dropped to ρ=0.318/ρ=0.329 (P<0.05/P<0.01), respectively for Abbott and vanished for Roche. As a result, only a maximum of 11% of NT titer variability could be explained by NC-antibody levels.ConclusionsOur data suggest that the apparent correlation between NC antibodies and NT titers is strongly mediated by co-occurring RBD antibody concentrations. To avoid falsely implied causal relationships, all correlation analyses of non-spike-associated antibody assays and neutralization assays should include a partial correlation analysis to exclude a possible mediator effect of spike-associated antibodies.

scholarly journals Donor Anti-Spike Immunity is Related to Recipient Recovery and Can Predict the Efficacy of Convalescent Plasma Units.

2021 ◽  
Author(s):  
Sanath Kumar Janaka ◽  
William Hartman ◽  
HuiHui Mou ◽  
Michael Frazan ◽  
Susan L Stramer ◽  
...  
Keyword(s):  
Passive Immunization ◽  
Therapeutic Benefit ◽  
Spike Protein ◽  
Plasma Samples ◽  
Viral Neutralization ◽  
Neutralizing Activity ◽  
Novel Coronavirus ◽  
Option Selection ◽  
Antibody Levels ◽  
Design And Methods

Background: The novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP. Study design and methods: To identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients. Results: Viral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients. Conclusions: Since viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.

scholarly journals A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and antibody cross reactions

2020 ◽  
Author(s):  
Eric Laing ◽  
Spencer Sterling ◽  
Stephanie Richard ◽  
Nusrat Epsi ◽  
Shreshta Phogat ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Human Subject ◽  
Spike Protein ◽  
Igg Antibody ◽  
Memory Response ◽  
Cross Reactions ◽  
Antibody Assays ◽  
Antibody Levels ◽  
Simultaneous Identification ◽  
Microsphere Immunoassay

Abstract Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we developed and applied a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human betacoronaviruses, HCoV-HKU1 and HCoV-OC43, that enables measurement of off-target pre-existing cross-reactive antibodies. The MMIA performances characteristics are: 98% sensitive and 100% specific for human subject samples collected as early as 10 days from symptom onset. The MMIA permitted the simultaneous identification of SARS-CoV-2 seroconversion and the induction of SARS-CoV-2 IgG antibody cross reactions to SARS-CoV-1 and MERS-CoV. Further, synchronous increases of HCoV-OC43 IgG antibody levels was detected with SARS-CoV-2 seroconversion in a subset of subjects for whom early infection sera were available prior to their SARS-CoV-2 seroconversion, suggestive of an HCoV-OC43 memory response triggered by SARS-CoV-2 infection.

scholarly journals The First National Survey of Cadmium in Cacao Farm Soil in Colombia

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 761
Author(s):  
Daniel Bravo ◽  
Clara Leon-Moreno ◽  
Carlos Alberto Martínez ◽  
Viviana Marcela Varón-Ramírez ◽  
Gustavo Alfonso Araujo-Carrillo ◽  
...  
Keyword(s):  
Graphical Models ◽  
Partial Correlation ◽  
National Level ◽  
Prediction Method ◽  
Correlation Coefficients ◽  
Predictive Performance ◽  
Nationwide Survey ◽  
Critical Discussion ◽  
Cadmium Content ◽  
Soil Variables

This study represents the first nationwide survey regarding the distribution of Cd content in cacao-growing soils in Colombia. The soil Cd distribution was analyzed using a cold/hotspots model. Moreover, both descriptive and predictive analytical tools were used to assess the key factors regulating the Cd concentration, considering Cd content and eight soil variables in the cacao systems. A critical discussion was performed in four main cacao-growing districts. Our results suggest that the performance of a model using all the variables will always be superior to the one using Zn alone. The analyzed variables featured an appropriate predictive performance, nonetheless, that performance has to be improved to develop a prediction method that might be used nationwide. Results from the fitted graphical models showed that the largest associations (as measured by the partial correlation coefficients) were those between Cd and Zn. Ca had the second-largest partial correlation with Cd and its predictive performance ranked second. Interestingly, it was found that there was a high variability in the factors correlated with Cd in cacao growing soils at a national level. Therefore, this study constitutes a baseline for the forthcoming studies in the country and should be reinforced with an analysis of cadmium content in cacao beans.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

scholarly journals Performance of a SARS CoV-2 antibody ELISA based on simultaneous measurement of antibodies against the viral nucleoprotein and receptor-binding domain

2021 ◽  
Author(s):  
Nina Reiners ◽  
Carolin Schnurra ◽  
Henning Trawinski ◽  
Judith Kannenberg ◽  
Thomas Hermsdorf ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Simultaneous Measurement ◽  
False Positives ◽  
Binding Domain ◽  
Diagnostic Sensitivity ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Simultaneous Testing ◽  
Antibody Assays ◽  
Antibody Elisa

AbstractSARS CoV-2 antibody assays measure antibodies against the viral nucleoprotein (NP) or spike protein. The study examined if testing of antibodies against both antigens increases the diagnostic sensitivity. Sera (N=98) from infected individuals were tested with ELISAs based on the NP, receptor-binding domain (RBD), or both proteins. The AUROCs were 0.958 (NP), 0.991 (RBD), and 0.992 (NP/RBD). The RBD- and NP/RBD-based ELISAs showed better performance than the NP-based assay. Simultaneous testing for antibodies against NP and RBD increased the number of true and false positives. If maximum diagnostic sensitivity is required, the NP/RBD-based ELISA is preferable. Otherwise, the RBD-based ELISA is sufficient.

SERUM GONADOTROPHINS, TESTOSTERONE AND SPERMATOGENESIS IN SUBFERTILE MEN

1977 ◽  
Vol 86 (3) ◽  
pp. 651-658 ◽  
Author(s):  
J. H. Aafjes ◽  
J. C. M. van der Vijver ◽  
R. Docter ◽  
P. E. Schenck
Keyword(s):  
Partial Correlation ◽  
Sperm Count ◽  
Correlation Coefficients ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
The Other ◽  
Sperm Production ◽  
Positive Correlation ◽  
Natural Logarithm ◽  
Biopsy Score

ABSTRACT In 210 subfertile men there existed a significant positive correlation between serum FSH and LH (0.41). No correlation was observed between the gonadotrophin levels and testosterone. In contrast to this FSH as well as LH were negatively correlated with the natural logarithm (In) of the sperm count/ml ejaculate (−0.44 and −0.18, respectively). When the positive correlation which existed between FSH and LH was used to calculate partial correlation coefficients, the coefficient between FSH and ln sperm count did hardly change (−0.41) the coefficient between LH and ln sperm count on the other hand became insignificant (−0.05). This suggests that spermatogenesis influences FSH serum levels in subfertile men by a decreased suppression when sperm production is diminished. Testicular biopsies taken from 97 of these patients were used to determine biopsy scores. These scores showed a significant negative correlation with FSH (−0.34) and a positive one with ln sperm count/ml ejaculate (0.45). Interestingly the biopsy score of 16 patients who fertilized their wives, was found to be higher compared with the score of the other patients who did not fertilize. The number of sperm/ml ejaculate and the FSH values of these 2 groups of biopsied patients were, however, not significantly different. This leads to the conclusion that the biopsy score is a better parameter for the evaluation of oligospermic men than either sperm count or FSH serum values.

scholarly journals 480 Preliminary evaluation of a novel coronavirus vaccine (CORVax) using electroporation of plasmid DNA encoding a stabilized prefusion SARS-CoV-2 spike protein alone or with transfection of plasmid IL-12

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A514-A514
Author(s):  
Shawn Jensen ◽  
Christopher Twitty ◽  
Christopher Paustian ◽  
Madelein Laws ◽  
Glenna McDonnell ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Binding Domain ◽  
Tumor Rejection ◽  
Spike Protein ◽  
Preliminary Evaluation ◽  
List Type ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Viral Neutralization

BackgroundSARS-CoV-2 (CoV2) has precipitated a global pandemic and the effectiveness of standard vaccine strategies to induce potent and persistent immunity to CoV2 is in question, particularly for the elderly. This problem is not dissimilar to what we have struggled with in our quest to induce immunity to cancer antigens, where vaccine-induced anti-cancer immune responses can be weak. Here, we describe a novel vaccine approach which leverages electroporation (EP) of a plasmid encoding a prefusion stabilized CoV2 spike protein (CORVax). As IL-12 has been shown to augment the efficacy of immunotherapy in aged mice,1 we have initiated studies to evaluate if plasmid IL-12 (TAVO™) can similarly augment anti-CoV2 immune responses in young mice and have planned studies in aged animals.MethodsA prefusion stabilized CoV2 spike plasmid expression vector was constructed, a master cell bank generated and clinical-grade plasmid manufactured. C57BL/6 and BALB/c were vaccinated via intramuscular (IM) and/or intradermal (ID) injection followed immediately by EP of plasmids encoding the CoV2 spike protein with or without plasmid-encoded murine IL-12 on days 1 and 14 or 21. Mice were followed for >120 days to assess safety. Splenocytes and serum were harvested at different time points to interrogate virus-specific cellular responses as well anti-spike IgG1/IgG2 antibody titers. A surrogate viral neutralization test (sVNT) assessed serum blockade of soluble hACE2R binding to immobilized CoV2 spike.ResultsPreliminary data shows that EP of CORVax alone or combined with IL-12 was safe. EP of CORVax was able to elicit anti-Spike IgG antibodies (IC50 = 1/2112), as well as IgG antibodies targeting the receptor binding domain of the Spike protein (IC50 = 1/965) approximately 40 days after the booster vaccination. In 2 of 2 experiments, CORVax combined with IL-12 significantly (P<0.0001) increased the sVNT titers at 2 months, but this benefit was lost by 3 months.ConclusionsEarly preclinical data shows that EP of CORVax can induce IgG responses to CoV2 Spike and the receptor binding domain (RBD) as well as apparent viral neutralizing activity. The addition of IL-12, at least transiently, increased sVNT titer. We plan to investigate alternate vaccine boosting strategies while extending these studies into aged animals and initiate a clinical trial in the near future.ReferencesRuby CE, Weinberg AD. OX40-Enhanced tumor rejection and effector T cell differentiation decreases with age. J Immunol2009;182:1481–9. https://doi.org/10.4049/jimmunol.182.3.1481.

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