EVALUATION OF QUANTITATIVE AND QUALITATIVE CHARACTERISTICS OF IMMUNE RESPONSES INDUCED BY IMMUNODOMINANT B-CELL EPITOPES WITHIN VIRULENT SURFACE PROTEINS OF S. PNEUMONIAE IN MICE

2016 ◽  
Author(s):  
Theodora Papastamatiou
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Surface Proteins ◽  
B Cell Epitopes ◽  
Qualitative Characteristics

scholarly journals Immunological Responses to the Relapsing Fever SpirocheteBorrelia turicataein Infected Rhesus Macaques: Implications for Pathogenesis and Diagnosis

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Monica E. Embers ◽  
Aparna Krishnavajhala ◽  
Brittany A. Armstrong ◽  
Michael W. Curtis ◽  
Bapi Pahar ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Rhesus Macaques ◽  
Surface Proteins ◽  
Vaccine Antigen ◽  
Global Public Health ◽  
Relapsing Fever ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACTThe global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques withBorrelia turicatae(a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate thatB. turicataeelicits from peripheral blood cells key inflammatory response mediators (interleukin-1β and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.

scholarly journals Immunoinformatic Approach for the identification of T Cell and B Cell Epitopes in the Surface Glycoprotein and Designing a Potent Multiepitope Vaccine Construct Against SARS-CoV-2 including the new UK variant

2021 ◽  
Author(s):  
Kaveri Krishnasamy ◽  
Gracy Fathima Selvaraj ◽  
Kiruba Ramesh ◽  
Padmaoriya Padmanabhan ◽  
Vidya Gopalan ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
T Lymphocyte ◽  
Vaccine Candidate ◽  
Surface Glycoprotein ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
New Variant

The emergence of a novel coronavirus in China in late 2019 has turned into a SARS-CoV-2 pandemic affecting several millions of people worldwide in a short span of time with high fatality. The crisis is further aggravated by the emergence and evolution of new variant SARS-CoV-2 strains in UK during December, 2020 followed by their transmission to other countries. A major concern is that prophylaxis and therapeutics are not available yet to control and prevent the virus which is spreading at an alarming rate, though several vaccine trials are in the final stage. As vaccines are developed through various strategies, their immunogenic potential may drastically vary and thus pose several challenges in offering both arms of immunity such as humoral and cell-mediated immune responses against the virus. In this study, we adopted an immunoinformatics-aided identification of B cell and T cell epitopes in the Spike protein, which is a surface glycoprotein of SARS-CoV-2, for developing a new Multiepitope vaccine construct (MEVC). MEVC has 575 amino acids and comprises adjuvants and various cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes that possess the highest affinity for the respective HLA alleles, assembled and joined by linkers. The computational data suggest that the MEVC is non-toxic, non-allergenic and thermostable with the capability to elicit both humoral and cell-mediated immune responses. The population coverage of various countries affected by COVID-19 with respect to the selected B and T cell epitopes in MEVC was also investigated. Subsequently, the biological activity of MEVC was assessed by bioinformatic tools using the interaction between the vaccine candidate and the innate immune system receptors TLR3 and TLR4. The epitopes of the construct were analyzed with that of the strains belonging to various clades including the new variant UK strain having multiple unique mutations in S protein. Due to the advantageous features, the MEVC can be tested in vitro for more practical validation and the study offers immense scope for developing a potential vaccine candidate against SARS-CoV-2 in view of the public health emergency associated with COVID-19 disease caused by SARS-CoV-2.

scholarly journals Evaluation of Protective Efficacy of Selected Immunodominant B-Cell Epitopes within Virulent Surface Proteins of Streptococcus pneumoniae

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Theodora Papastamatiou ◽  
John G. Routsias ◽  
Olga Koutsoni ◽  
Eleni Dotsika ◽  
Athanassios Tsakris ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
B Cell ◽  
Protective Efficacy ◽  
Surface Proteins ◽  
Lethal Challenge ◽  
Hyperimmune Serum ◽  
B Cell Epitopes ◽  
Content Type ◽  
Binding Domains

ABSTRACT Four previously identified immunodominant B-cell epitopes, located within known virulent pneumococcal proteins CbpD, PhtD, PhtE, and ZmpB, had shown promising in vivo immunological characteristics, indicating their potential to be used as vaccine antigens. In this study, we further evaluated the opsonophagocytic activity of antibodies against these epitopes and their capacity to protect mice from pneumococcal sepsis. An opsonophagocytic killing assay (OPKA) revealed that OPKA titers of human anti-peptide antibodies against pneumococcal serotypes 1, 3, and 19A were significantly higher ( P < 0.001) than those of the control sera, suggesting their functional potential against virulent clinical isolates. Data obtained from mice actively immunized with any of the selected epitope analogues or with a mixture of these (G_Mix group) showed, compared to controls, enhanced survival against the highly virulent pneumococcal serotype 3 ( P < 0.001). Moreover, passive transfer of hyperimmune serum from G_Mix to naive mice also conferred protection to a lethal challenge with serotype 3, which demonstrates that the observed protection was antibody mediated. All immunized murine groups elicited gradually higher antibody titers and avidity, suggesting a maturation of immune response over time. Among the tested peptides, PhD_pep19 and PhtE_pep40 peptides, which reside within the zinc-binding domains of PhtD and PhtE proteins, exhibited superior immunological characteristics. Recently it has been shown that zinc uptake is of high importance for the virulence of Streptococcus pneumoniae ; thus, our findings suggest that these epitopes deserve further evaluation as novel immunoreactive components for the development of a polysaccharide-independent pneumococcal vaccine.

scholarly journals Shotgun Immunoproteomic Approach for the Discovery of Linear B-Cell Epitopes in Biothreat Agents Francisella tularensis and Burkholderia pseudomallei

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrik D’haeseleer ◽  
Nicole M. Collette ◽  
Victoria Lao ◽  
Brent W. Segelke ◽  
Steven S. Branda ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Francisella Tularensis ◽  
Burkholderia Pseudomallei ◽  
Outer Membrane Proteins ◽  
Screening Method ◽  
Cost Effective ◽  
Immune Memory ◽  
B Cell Epitopes ◽  
Linear Epitopes

Peptide-based subunit vaccines are coming to the forefront of current vaccine approaches, with safety and cost-effective production among their top advantages. Peptide vaccine formulations consist of multiple synthetic linear epitopes that together trigger desired immune responses that can result in robust immune memory. The advantages of linear compared to conformational epitopes are their simple structure, ease of synthesis, and ability to stimulate immune responses by means that do not require complex 3D conformation. Prediction of linear epitopes through use of computational tools is fast and cost-effective, but typically of low accuracy, necessitating extensive experimentation to verify results. On the other hand, identification of linear epitopes through experimental screening has been an inefficient process that requires thorough characterization of previously identified full-length protein antigens, or laborious techniques involving genetic manipulation of organisms. In this study, we apply a newly developed generalizable screening method that enables efficient identification of B-cell epitopes in the proteomes of pathogenic bacteria. As a test case, we used this method to identify epitopes in the proteome of Francisella tularensis (Ft), a Select Agent with a well-characterized immunoproteome. Our screen identified many peptides that map to known antigens, including verified and predicted outer membrane proteins and extracellular proteins, validating the utility of this approach. We then used the method to identify seroreactive peptides in the less characterized immunoproteome of Select Agent Burkholderia pseudomallei (Bp). This screen revealed known Bp antigens as well as proteins that have not been previously identified as antigens. Although B-cell epitope prediction tools Bepipred 2.0 and iBCE-EL classified many of our seroreactive peptides as epitopes, they did not score them significantly higher than the non-reactive tryptic peptides in our study, nor did they assign higher scores to seroreactive peptides from known Ft or Bp antigens, highlighting the need for experimental data instead of relying on computational epitope predictions alone. The present workflow is easily adaptable to detecting peptide targets relevant to the immune systems of other mammalian species, including humans (depending upon the availability of convalescent sera from patients), and could aid in accelerating the discovery of B-cell epitopes and development of vaccines to counter emerging biological threats.

scholarly journals SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design

2020 ◽  
Author(s):  
Sandeep Kumar Kushwaha ◽  
Veerbhan Kesarwani ◽  
Samraggi Choudhury ◽  
Sonu Gandhi ◽  
Shailesh Sharma
Keyword(s):  
Molecular Docking ◽  
Immune Responses ◽  
B Cell ◽  
Cell Lines ◽  
Docking Studies ◽  
B Cell Receptors ◽  
B Cell Epitopes ◽  
Cell Receptors ◽  
Molecular Docking Studies ◽  
Mhc Molecules

AbstractSARS-CoV-2 is a single-stranded RNA virus that has caused more than 0.29 million deaths worldwide as of May 2020, and influence of COVID-19 pandemic is increasing continuously in the absence of approved vaccine and drug. Moreover, very limited information is available about SARS-CoV-2 expressed regions and immune responses. In this paper an effort has been made, to facilitate vaccine development by proposing multiple epitopes as potential vaccine candidates by utilising SARS-CoV-2 transcriptome data. Here, publicly available RNA-seq data of SARS-CoV-2 infection in NHBE and A549 human cell lines were used to construct SARS-CoV-2 transcriptome to understand disease pathogenesis and immune responses. In the first step, epitope prediction, MHC class I and II gene identification for epitopes, population coverage, antigenicity, immunogenicity, conservation and crossreactivity analysis with host antigens were performed by using SARS-CoV-2 transcriptome, and in the second step, structural compatibility of identified T-and B-cell epitopes were evaluated with MHC molecules and B-cell receptors through molecular docking studies. Quantification of MHC gene expression was also performed that indicated high variation in allele types and expression level of MHC genes with respect to cell lines. In A549 cell line, HLA-A*30:01:01:01 and HLA-B*44:03:01:01 were highly expressed, whereas 92 variants of HLA-A*24 genes such as HLA-A*24:02:01:01, HLA-A*24:286, HLA-A*24:479Q, HLA-A*24:02:134 and HLA-A*24:02:116 were highly expressed in NHBE cell lines. Prevalence of HLA-A*24 alleles was suggested as risk factors for H1N1 infection, and associated with type-1 diabetes. HLA-C*03:03, linked with male infertility factors was also highly expressed in SARS-CoV-2 infected NHBE cell lines. Finally, three potential T-cell and five B-cell epitopes were selected for molecular docking studies with twenty-two MHC molecules and two B-cell receptors respectively. The results of in silico analysis indicated that proposed epitopes have high potential to recognize immune response of SARS-CoV-2 infection. This study will facilitate in vitro and in vivo vaccine related research studies.

scholarly journals High-resolution profiling of linear B-cell epitopes from mucin-associated surface proteins (MASPs) of Trypanosoma cruzi during human infections

2017 ◽  
Vol 11 (9) ◽  
pp. e0005986 ◽  
Author(s):  
Ignacio M. Durante ◽  
Pablo E. La Spina ◽  
Santiago J. Carmona ◽  
Fernán Agüero ◽  
Carlos A. Buscaglia
Keyword(s):  
High Resolution ◽  
Trypanosoma Cruzi ◽  
B Cell ◽  
Surface Proteins ◽  
B Cell Epitopes ◽  
Human Infections ◽  
Linear B

scholarly journals Yersinia pestis Antigen F1 but Not LcrV Induced Humoral and Cellular Immune Responses in Humans Immunized with Live Plague Vaccine—Comparison of Immunoinformatic and Immunological Approaches

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 698
Author(s):  
Valentina A. Feodorova ◽  
Anna M. Lyapina ◽  
Maria A. Khizhnyakova ◽  
Sergey S. Zaitsev ◽  
Yury V. Saltykov ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Yersinia Pestis ◽  
In Silico ◽  
Rational Design ◽  
Limited Information ◽  
B Cell Epitopes ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Plague Vaccine

The recent progress in immunoinformatics provided the basis for an accelerated development of target-specific peptide vaccines as an alternative to the traditional vaccine concept. However, there is still limited information on whether the in silico predicted immunoreactive epitopes correspond to those obtained from the actual experiments. Here, humoral and cellular immune responses to two major Yersinia pestis protective antigens, F1 and LcrV, were studied in human donors immunized with the live plague vaccine (LPV) based on the attenuated Y. pestis strain EV line NIIEG. The F1 antigen provided modest specific cellular (mixed T helper 1 (Th1)/Th2 type) and humoral immune responses in vaccinees irrespective of the amount of annual vaccinations and duration of the post-vaccination period. The probing of the F1 overlapping peptide library with the F1-positive sera revealed the presence of seven linear B cell epitopes, which were all also predicted by in silico assay. The immunoinformatics study evaluated their antigenicity, toxicity, and allergenic properties. The epitope TSQDGNNH was mostly recognized by the sera from recently vaccinated donors rather than antibodies from those immunized decades ago, suggesting the usefulness of this peptide for differentiation between recent and long-term vaccinations. The in silico analysis predicted nine linear LcrV-specific B-cell epitopes; however, weak antibody and cellular immune responses prevented their experimental evaluation, indicating that LcrV is a poor marker of successful vaccination. No specific Th17 immune response to either F1 or LcrV was detected, and there were no detectable serum levels of F1-specific immunoglobulin A (IgA) in vaccinees. Overall, the general approach validated in the LPV model could be valuable for the rational design of vaccines against other neglected and novel emerging infections with high pandemic potency.

Identification of B cell epitopes recognized by antibodies specific for the tumor antigen NY-ESO-1 in cancer patients with spontaneous immune responses

2005 ◽  
Vol 117 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Danila Valmori ◽  
Naira E. Souleimanian ◽  
Charles S. Hesdorffer ◽  
Gerd Ritter ◽  
Lloyd J. Old ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cancer Patients ◽  
Tumor Antigen ◽  
B Cell Epitopes

scholarly journals Shotgun Immunoproteomic Approach for the Discovery of Linear B Cell Epitopes in Biothreat Agents Francisella tularensis and Burkholderia pseudomallei

2021 ◽  
Author(s):  
Patrik D'haeseleer ◽  
Nicole M Collette ◽  
Victoria Lao ◽  
Brent W Segelke ◽  
Steven S Branda ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Francisella Tularensis ◽  
Burkholderia Pseudomallei ◽  
Outer Membrane Proteins ◽  
Screening Method ◽  
Immune Memory ◽  
B Cell Epitopes ◽  
Peptide Epitopes ◽  
Linear Epitopes

Peptide-based subunit vaccines are coming to the forefront of current vaccine approaches, with safety and cost-effective production among their top advantages. Peptide vaccine formulations consist of multiple synthetic linear epitopes that together trigger desired immune responses that can result in robust immune memory. The advantages of peptide epitopes are their simple structure, ease of synthesis, and ability to stimulate immune responses by means that do not require complex 3D conformation. Identification of linear epitopes is currently an inefficient process that requires thorough characterization of previously identified full-length protein antigens, or laborious techniques involving genetic manipulation of organisms. In this study, we apply a newly developed generalizable screening method that enables efficient identification of B cell epitopes in the proteomes of pathogenic bacteria. As a test case, we used this method to identify epitopes in the proteome of Francisella tularensis (Ft), a Select Agent with a well-characterized immunoproteome. Our screen identified many peptides that map to known antigens, including verified and predicted outer membrane proteins and extracellular proteins, validating the utility of this approach. We then used the method to identify seroreactive peptides in the less characterized immunoproteome of Select Agent Burkholderia pseudomallei (Bp). This screen revealed known Bp antigens as well as proteins that have not been previously identified as antigens. The present workflow is easily adaptable to detecting peptide targets relevant to the immune systems of other mammalian species, including humans (depending upon the availability of convalescent sera from patients), and could aid in accelerating the discovery of B cell epitopes and development of vaccines to counter emerging biological threats.

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