scholarly journals FluKB: A Knowledge-Based System for Influenza Vaccine Target Discovery and Analysis of the Immunological Properties of Influenza Viruses

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Christian Simon ◽  
Ulrich J. Kudahl ◽  
Jing Sun ◽  
Lars Rønn Olsen ◽  
Guang Lan Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
B Cell ◽  
Keyword Search ◽  
Automatic Generation ◽  
Influenza Viruses ◽  
Cell Vaccine ◽  
Knowledge Based System ◽  
Knowledge Based ◽  
Analytical Tools

FluKB is a knowledge-based system focusing on data and analytical tools for influenza vaccine discovery. The main goal of FluKB is to provide access to curated influenza sequence and epitope data and enhance the analysis of influenza sequence diversity and the analysis of targets of immune responses. FluKB consists of more than 400,000 influenza protein sequences, known epitope data (357 verified T-cell epitopes, 685 HLA binders, and 16 naturally processed MHC ligands), and a collection of 28 influenza antibodies and their structurally defined B-cell epitopes. FluKB was built using a modular framework allowing the implementation of analytical workflows and includes standard search tools, such as keyword search and sequence similarity queries, as well as advanced tools for the analysis of sequence variability. The advanced analytical tools for vaccine discovery include visual mapping of T- and B-cell vaccine targets and assessment of neutralizing antibody coverage. FluKB supports the discovery of vaccine targets and the analysis of viral diversity and its implications for vaccine discovery as well as potential T-cell breadth and antibody cross neutralization involving multiple strains. FluKB is representation of a new generation of databases that integrates data, analytical tools, and analytical workflows that enable comprehensive analysis and automatic generation of analysis reports.

Impaired Specific B-Cell While Preserved T-Cell Response Against Influenza Vaccine in SOT Recipients.

2014 ◽  
Vol 98 ◽  
pp. 188
Author(s):  
D. Zbinden ◽  
M. Pascual ◽  
S. Lartey ◽  
R. Pathirana ◽  
G. Bredholt ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
B Cell ◽  
Cell Response ◽  
T Cell Response

scholarly journals Transfer of influenza vaccine–primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Edward A. Stadtmauer ◽  
Dan T. Vogl ◽  
Eline Luning Prak ◽  
Jean Boyer ◽  
Nicole A. Aqui ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Influenza Vaccine ◽  
B Cell ◽  
Cell Transplantation ◽  
Study Endpoint ◽  
Cell Product ◽  
Cell Immunity

Abstract Severe immune deficiency follows autologous stem cell transplantation for multiple myeloma and is associated with significant infectious morbidity. This study was designed to evaluate the utility of a pretransplantation vaccine and infusion of a primed autologous T-cell product in stimulating specific immunity to influenza. Twenty-one patients with multiple myeloma were enrolled from 2007 to 2009. Patients were randomly assigned to receive an influenza-primed autologous T-cell product or a nonspecifically primed autologous T-cell product. The study endpoint was the development of hemagglutination inhibition titers to the strain-specific serotypes in the influenza vaccine. Enzyme-linked immunospot assays were performed to confirm the development of influenza-specific B-cell and T-cell immunity. Patients who received the influenza-primed autologous T-cell product were significantly more likely to seroconvert in response to the influenza vaccine (P = .001). Seroconversion was accompanied by a significant B-cell response. No differences were observed in the global quantitative recovery of T-cell and B-cell subsets or in global T-cell and B-cell function. The provision of a primed autologous T-cell product significantly improved subsequent influenza vaccine responses. This trial was registered at www.clinicaltrials.gov as #NCT00499577.

scholarly journals Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8+ T-Cell Responses

2009 ◽  
Vol 84 (4) ◽  
pp. 1847-1855 ◽  
Author(s):  
Scott N. Mueller ◽  
William A. Langley ◽  
Elena Carnero ◽  
Adolfo García-Sastre ◽  
Rafi Ahmed
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
B Cell ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Influenza Viruses ◽  
Wild Type Virus ◽  
Virus Infections ◽  
Cell Responses ◽  
B Cell Responses

ABSTRACT The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8+ T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8+ T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.

scholarly journals Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model

2021 ◽  
Vol 9 (2) ◽  
pp. 259
Author(s):  
Ekaterina Stepanova ◽  
Elena Krutikova ◽  
Pei-Fong Wong ◽  
Victoria Matyushenko ◽  
Ekaterina Bazhenova ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Type A ◽  
Influenza Viruses ◽  
Effector Memory ◽  
Influenza B Virus ◽  
Influenza B ◽  
Live Attenuated Influenza Vaccine ◽  
B Virus

Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required.

scholarly journals Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants

2021 ◽  
Author(s):  
Anni Ge ◽  
Melissa Rioux ◽  
Alyson Ann Kelvin
Keyword(s):  
T Cell ◽  
B Cell ◽  
Glycosylation Site ◽  
Viral Escape ◽  
Spike Protein ◽  
Immune Memory ◽  
Cell Vaccine ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Cell Immunity

Since its emergence into the human population at the end of 2019, SARS-CoV-2 has caused significant morbidity and mortality worldwide. Efforts to develop a protective vaccine against COVID-19 have yielded several vaccine platforms currently in distribution targeting the original SARS-CoV-2 spike protein sequence from the first cases of infection. In recent months, variants of SARS-CoV-2 have raised concerns that viral mutation may undermine vaccination efforts through viral escape of host immune memory acquired from infection or vaccination. We therefore used a computational approach to predict changes in spike protein antigenicity with respect to host B cell and CD8+ T cell immunity across six SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, P.1, B.1.429, and mink-related). Our epitope analysis using DiscoTope suggests possible changes in B cell epitopes in the S1 region of the spike protein across variants, in particular the B.1.1.7 and B.1.351 lineages, which may influence immunodominance. Additionally, we show that high-affinity MHC-I-binding peptides and glycosylation sites on the spike protein appear consistent between variants with the exception of an extra glycosylation site in the P.1 variant. Together, these analyses suggests T cell vaccine strategies have the most longevity before reformulation.

scholarly journals Mosaic H5 Hemagglutinin Provides Broad Humoral and Cellular Immune Responses against Influenza Viruses

2016 ◽  
Vol 90 (15) ◽  
pp. 6771-6783 ◽  
Author(s):  
Attapon Kamlangdee ◽  
Brock Kingstad-Bakke ◽  
Jorge E. Osorio
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Dna Vaccine ◽  
Influenza Viruses ◽  
Effective Protection ◽  
Cell Responses ◽  
Mosaic Approach

ABSTRACTThe most effective way to prevent influenza virus infection is via vaccination. However, the constant mutation of influenza viruses due to antigenic drift and shift compromises vaccine efficacy. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. Using the modified vaccinia Ankara (MVA) virus, we had previously generated a recombinant vaccine against highly pathogenic avian influenza virus (H5N1) based on anin silicomosaic approach. This MVA-H5M construct protected mice against multiple clades of H5N1 and H1N1 viruses. We have now further characterized the immune responses using immunodepletion of T cells and passive serum transfer, and these studies indicate that antibodies are the main contributors in homosubtypic protection (H5N1 clades). Compared to a MVA construct expressing hemagglutinin (HA) from influenza virus A/VN/1203/04 (MVA-HA), the MVA-H5M vaccine markedly increased and broadened B cell and T cell responses against H5N1 virus. The MVA-H5M also provided effective protection with no morbidity against H5N1 challenge, whereas MVA-HA-vaccinated mice showed clinical signs and experienced significant weight loss. In addition, MVA-H5M induced CD8+T cell responses that play a major role in heterosubtypic protection (H1N1). Finally, expression of the H5M gene as either a DNA vaccine or a subunit protein protected mice against H5N1 challenge, indicating the effectiveness of the mosaic sequence without viral vectors for the development of a universal influenza vaccine.IMPORTANCEInfluenza viruses infect up to one billion people around the globe each year and are responsible for 300,000 to 500,000 deaths annually. Vaccines are still the main intervention to prevent infection, but they fail to provide effective protection against heterologous strains of viruses. We developed broadly reactive H5N1 vaccine based on anin silicomosaic approach and previously demonstrated that modified vaccinia Ankara expressing an H5 mosaic hemagglutinin prevented infection with multiple clades of H5N1 and limited severe disease after H1N1 infection. Further characterization revealed that antibody responses and T cells are main contributors to protection against H5N1 and H1N1 viruses, respectively. The vaccine also broadens both T cell and B cell responses compared to native H5 vaccine from influenza virus A/Vietnam/1203/04. Finally, delivering the H5 mosaic as a DNA vaccine or as a purified protein demonstrated effective protection similar to the viral vector approach.

scholarly journals Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

2020 ◽  
Author(s):  
Christof C. Smith ◽  
Sarah Entwistle ◽  
Caryn Willis ◽  
Steven Vensko ◽  
Wolfgang Beck ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epitope Mapping ◽  
Cell Epitope ◽  
Computational Prediction ◽  
Sequence Conservation ◽  
Cell Vaccine ◽  
T Cell Epitopes ◽  
Peptide Vaccines ◽  
B Cell Epitope

AbstractThere is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, such vaccines can be rapidly manufactured in a distributed manner. In this study, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2. We begin with an exploration of the space of possible T cell epitopes in SARS-CoV-2 with interrogation of predicted HLA-I and HLA-II ligands, overlap between predicted ligands, protein source, as well as concurrent human/murine coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles and co-localization of CD4+ and CD8+ T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials.Abstract Figure

scholarly journals A Fusion Protein Based on the Second Subunit of Hemagglutinin of Influenza A/H2N2 Viruses Provides Cross Immunity

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 116-126 ◽  
Author(s):  
L. A. Stepanova ◽  
M. V. Sergeeva ◽  
M. A. Shuklina ◽  
A. A. Shaldzhyan ◽  
M. V. Potapchuk ◽  
...  
Keyword(s):  
T Cell ◽  
Fusion Protein ◽  
B Cell ◽  
Influenza A ◽  
Wide Spectrum ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Recombinant Fusion Protein ◽  
Target Sequence ◽  
Th2 Response

Conserved fragments of the second subunit of hemagglutinin (HA2) are of great interest for the design of vaccine constructs that can provide protective immunity against influenza A viruses of different subtypes. A recombinant fusion protein, FlgMH, was constructed on the basis of flagellin and a highly conserved HA2 fragment (35-107) of influenza viruses of the subtype A/H2N2, containing B cell, CD4+ T cell, and CD8+ T cell epitopes. The native conformation of the HA2 fragment was partially preserved upon its attachment to the C-terminus of flagellin within the recombinant fusion protein FlgMH. FlgMH was shown to stimulate a mixed Th1/Th2 response of cross-reactive antibodies, which bind to influenza viruses of the first phylogenetic group (H1, H2, H5), to the target sequence as well as the induction of specific cytotoxic T cells (CD3+CD8+IFN+). Immunization with the recombinant protein protected animals from a lethal influenza infection. The developed FlgMH protein is a promising agent that may be included in an influenza vaccine with a wide spectrum of action which will be able to stimulate the T and B cell immune responses.

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