scholarly journals Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies

2021 ◽  
Vol 17 (12) ◽  
pp. e1009675
Author(s):  
Sarah A. Robinson ◽  
Matthew I. J. Raybould ◽  
Constantin Schneider ◽  
Wing Ki Wong ◽  
Claire Marks ◽  
...  
Keyword(s):  
Immune Responses ◽  
Structure Function ◽  
Specific Antibody ◽  
High Accuracy ◽  
Computational Method ◽  
Structural Modelling ◽  
High Confidence ◽  
Genetic Lineages ◽  
Functional Convergence ◽  
Therapeutic Sequence

Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. Sequence-based clonal clustering can identify antibodies with similar epitope complementarity, however, antibodies from markedly different lineages but with similar structures can engage the same epitope. We describe a novel computational method for epitope profiling based on structural modelling and clustering. Using the method, we demonstrate that sequence dissimilar but functionally similar antibodies can be found across the Coronavirus Antibody Database, with high accuracy (92% of antibodies in multiple-occupancy structural clusters bind to consistent domains). Our approach functionally links antibodies with distinct genetic lineages, species origins, and coronavirus specificities. This indicates greater convergence exists in the immune responses to coronaviruses than is suggested by sequence-based approaches. Our results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis.

scholarly journals Epitope profiling of coronavirus-binding antibodies using computational structural modelling

2021 ◽  
Author(s):  
Sarah A. Robinson ◽  
Matthew I. J. Raybould ◽  
Constantin Schneider ◽  
Wing Ki Wong ◽  
Claire Marks ◽  
...  
Keyword(s):  
Immune Responses ◽  
Specific Antibody ◽  
Computational Method ◽  
Binding Modes ◽  
Structural Modelling ◽  
Clustering Method ◽  
High Confidence ◽  
Genetic Lineages ◽  
Functional Convergence ◽  
Binding Antibody

Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. It is well-established in the literature that sequence-based clonal clustering can identify antibodies with similar epitope complementarity. However, there is growing evidence that antibodies from markedly different lineages but with similar structures can engage the same epitope with near-identical binding modes. Here, we describe a novel computational method for epitope profiling based on structural modelling and clustering, and show how it can identify sequence-dissimilar antibodies that engage the same epitope. We start by searching for evidence of structural conservation across the latest solved SARS-CoV-2—binding antibody crystal structures. Despite the relatively small number of solved structures, we find numerous examples of sequence-diverse but structurally-similar coronavirus-binding antibodies engaging the same epitope. We therefore developed a high-throughput structural modeling and clustering method to identify functionally-similar antibodies across the set of thousands of coronavirus-binding antibody sequences in the Coronavirus Antibody Database (CoV-AbDab). In the resulting multiple-occupancy structural clusters, 92% bind to consistent domains based on CoV-AbDab metadata. Our approach functionally links antibodies with distinct genetic lineages, species origins, and coronavirus specificities. This indicates greater convergence exists in the immune responses to coronaviruses than would be suggested by sequence-based approaches. Our results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis.

scholarly journals Development and validation of an assay for detection of Japanese Encephalitis virus specific antibody responses

2020 ◽  
Author(s):  
Pradeep Darshana Pushpakumara ◽  
Chandima Jeewandara ◽  
Laksiri Gomes ◽  
Yashodha Perera ◽  
Ananda Wijewickrama ◽  
...  
Keyword(s):  
Immune Responses ◽  
Japanese Encephalitis Virus ◽  
Disease Severity ◽  
Japanese Encephalitis ◽  
Specific Antibody ◽  
Encephalitis Virus ◽  
Antibody Responses ◽  
Specific Antibodies ◽  
Dengue Disease ◽  
Conserved Regions

AbstractBackgroundAlthough immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity.Methodology/Principal findings20 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N=30), those who were only immune to the JEV and not DENV (JEV+DENV-, N=30), those who were only immune to DENV(JEV-DENV+, N=30) and in those who were immune to both viruses (JEV+DENV+, N=30). 7/20 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV-and 30/30 JEV+DENV+individuals, and only 3/30 (10%) JEV-DENV+individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n=175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n=175) (OR 5.3, 95% CI 3.3 to 8.3).Conclusions/SignificanceAs our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.Author summaryBoth Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) co-circulate in the same geographical region and have a potential to modulate the immune responses to each other. However, due to the difficulty in identifying antibody responses specific to either virus due to the highly cross-reactive nature of virus-specific antibodies, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV-specific, DENV non cross-reactive antibody responses by identifying JEV-specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV-specific antibodies associates with dengue disease severity. 20 JEV-specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed. We found that seven peptides were highly immunogenic and specific to the JEV and we further evaluated the usefulness of an ELISA developed using these pools of peptides. We found that our in-house ELISA was found to be significantly more sensitive some of the existing commercial assays. As this assay appears to be highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.

scholarly journals A Least Squares Computational Method for the Scattering Amplitude

1988 ◽  
Vol 41 (1) ◽  
pp. 47 ◽  
Author(s):  
JN Das
Keyword(s):  
Least Squares ◽  
Numerical Computation ◽  
Scattering Amplitude ◽  
High Accuracy ◽  
Computational Method ◽  
Partial Support ◽  
Numerical Instabilities

A new least squares computational method for the scattering amplitude is proposed. This may be applied without difficulty to atomic and other scattering computations. The approach is expected to give converged results of high accuracy and also to be free from major numerical instabilities. As an example a numerical computation is carried out following the method and some results are presented in partial support of the claim.

From Bio-Based Cryopreservation Strategies To Structural Modelling: The Case Study of Fucopol and Its Scalability To Greater Structure-Function Understanding

Cryobiology ◽  
2021 ◽  
Vol 103 ◽  
pp. 184-185
Author(s):  
Bruno Guerreiro ◽  
Filomena Freitas ◽  
João Lima ◽  
Jorge Silva ◽  
Madalena Dionísio ◽  
...  
Keyword(s):  
Structure Function ◽  
Structural Modelling

Modified wavelet method for solving fractional variational problems

2020 ◽  
pp. 107754632093202
Author(s):  
Haniye Dehestani ◽  
Yadollah Ordokhani ◽  
Mohsen Razzaghi
Keyword(s):  
Error Analysis ◽  
Operational Matrix ◽  
Approximate Solutions ◽  
Variational Problems ◽  
High Accuracy ◽  
Construction Method ◽  
Computational Method ◽  
Wavelet Method ◽  
Fractional Variational Problems ◽  
Operational Matrix Of Integration

In this article, a newly modified Bessel wavelet method for solving fractional variational problems is considered. The modified operational matrix of integration based on Bessel wavelet functions is proposed for solving the problems. In the process of computing this matrix, we have tried to provide a high-accuracy operational matrix. We also introduce the pseudo-operational matrix of derivative and the dual operational matrix with the coefficient. Also, we investigate the error analysis of the computational method. In the examples section, the behavior of the approximate solutions with respect to various parameters involved in the construction method is tested to illustrate the efficiency and accuracy of the proposed method.

scholarly journals Sero-evaluation of Immune Responses to Vibrio cholerae in a Postelimination Setting

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Tai The Diep ◽  
Owen Jensen ◽  
Nguyen Van Thuong ◽  
Nguyen Thi Ngoc Nhi ◽  
Nguyen Ngoc Anh Thu ◽  
...  
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Specific Antibody ◽  
Public Health Problem ◽  
Antibody Testing ◽  
Southern Vietnam ◽  
Significant Public Health Problem ◽  
Significant Public Health ◽  
Clinical Surveillance ◽  
Blood Spot

Abstract Cholera remains a significant public health problem worldwide. In settings of declining incidence, serosurveillance may be used to augment clinical surveillance. We utilized dried blood spot sampling and cholera-specific antibody testing to examine the serologic profiles of vaccinated and unvaccinated children in southern Vietnam, where cholera was recently eliminated.

scholarly journals Comparison of the Immunogenicities and Cross-Lineage Efficacies of Live Attenuated Peste des Petits Ruminants Virus Vaccines PPRV/Nigeria/75/1 and PPRV/Sungri/96

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Sophia Hodgson ◽  
Katy Moffat ◽  
Holly Hill ◽  
John T. Flannery ◽  
Simon P. Graham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Severe Disease ◽  
Small Ruminants ◽  
Virus Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peste Des Petits Ruminants ◽  
Systematic Analysis ◽  
Genetic Lineages

ABSTRACTPeste des petits ruminants (PPR) is a severe disease of goats and sheep that is widespread in Africa, the Middle East, and Asia. Several effective vaccines exist for the disease, based on attenuated strains of the virus (PPRV) that causes PPR. While the efficacy of these vaccines has been established by use in the field, the nature of the protective immune response has not been determined. In addition, while the vaccine derived from PPRV/Nigeria/75/1 (N75) is used in many countries, those developed in India have never been tested for their efficacy outside that country. We have studied the immune response in goats to vaccination with either N75 or the main Indian vaccine, which is based on isolate PPRV/India/Sungri/96 (S96). In addition, we compared the ability of these two vaccines, in parallel, to protect animals against challenge with pathogenic viruses from the four known genetic lineages of PPRV, representing viruses from different parts of Africa, as well as Asia. These studies showed that, while N75 elicited a stronger antibody response than S96, as measured by both enzyme-linked immunosorbent assay and virus neutralization, S96 resulted in more pronounced cellular immune responses, as measured by virus antigen-induced proliferation and interferon gamma production. While both vaccines induced comparable numbers of PPRV-specific CD8+T cells, S96 induced a higher number of CD4+T cells specifically responding to virus. Despite these quantitative and qualitative differences in the immune responses following vaccination, both vaccines gave complete clinical protection against challenge with all four lineages of PPRV.IMPORTANCEDespite the widespread use of live attenuated PPRV vaccines, this is the first systematic analysis of the immune response elicited in small ruminants. These data will help in the establishment of the immunological determinants of protection, an important step in the development of new vaccines, especially DIVA vaccines using alternative vaccination vectors. This study is also the first controlled test of the ability of the two major vaccines used against virulent PPRV strains from all genetic lineages of the virus, showing conclusively the complete cross-protective ability of these vaccines.

scholarly journals Impaired Gamma Interferon Responses against Parvovirus B19 by Recently Infected Children

2000 ◽  
Vol 74 (21) ◽  
pp. 9903-9910 ◽  
Author(s):  
Amanda Corcoran ◽  
Sean Doyle ◽  
David Waldron ◽  
Alfred Nicholson ◽  
Bernard P. Mahon
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Specific Antibody ◽  
Parvovirus B19 ◽  
Gamma Interferon ◽  
Capsid Proteins ◽  
Exact Nature ◽  
Unique Region ◽  
Antibody Reactivity ◽  
Ifn Γ

ABSTRACT Parvovirus B19 is the causative agent of “fifth disease” of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products. There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-mediated immune response is unclear. Immune responses to purified virus capsid proteins, VP1 and VP2, were examined from a cohort of recently infected children and compared with responses from long-term convalescent volunteers. The results demonstrate that antibody reactivity is primarily maintained against conformational epitopes in VP1 and VP2. The unique region of VP1 appears to be a major target for cell-mediated immune responses, particularly in recently infected individuals. We confirm that antibody reactivity against linear epitopes of VP2 is lost shortly after infection but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-γ). However, we observed a significant (P < 0.001) deficit in the production of IFN-γ in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid arthritis and unsuccessful pregnancy.

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