scholarly journals Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

2021 ◽  
Vol 16 (4) ◽  
Author(s):  
Fattaneh Sabzehali ◽  
Hossein Goudarzi ◽  
Alireza Salimi Chirani ◽  
Mohammad Hossein Yoosefi Izad ◽  
Mehdi Goudarzi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
T Lymphocyte ◽  
Tertiary Structure ◽  
Vaccine Candidate ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 4 ◽  
Health Concern ◽  
Effective Vaccine ◽  
Translation Efficiency ◽  
Ligand Interaction

Background: The emerging problem of antibiotic resistance in Pseudomonas aeruginosa is a global health concern; hence, revealing innovative therapeutic approaches (such as designing an immunogenic vaccine candidate) is needed. There is no evidence of the availability of an effective vaccine that can combat the infection caused by this microorganism. Objectives: This research was conducted to develop a potential chimeric vaccine against P. aeruginosa using reverse vaccinology approaches. Methods: The present vaccine candidate comprised outer membrane protein F and I (OprF/OprI) and PopB with appropriate linkers. After applying meticulous immune-informatics investigation, the multi-epitope vaccine was created, including helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), interferon gamma (IFN-γ), and interleukin 4 (IL-4) epitopes. Then, the physicochemical characteristics, allergenicity, toxicity, and antigenicity were analyzed. After investigating the secondary structure, the tertiary structure (3D) model was generated, refined, and validated via computational methods. Besides, the strong protein-ligand interaction and stability between the vaccine candidate and toll-like receptor 4 (TLR4) were determined via molecular docking and dynamics analyses. Moreover, in silico cloning accompanied by pET-22b (+) was used to achieve high translation efficiency. Results: Our results presumed that the chimeric-designed vaccine was thermostable and contained optimal physicochemical properties. This vaccine candidate was nontoxic and highly soluble and had stable protein and TLR4 interaction, adequately overexpressed in Escherichia coli. Overall, it could induce immune responses and repress this microorganism. Conclusions: Therefore, to inhibit Pseudomonas infections experimentally, the efficacy and safety of the vaccine design need to be validated.

scholarly journals Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2

2020 ◽  
Author(s):  
Viswajit Mulpuru ◽  
Nidhi Mishra
Keyword(s):  
T Lymphocyte ◽  
Vaccine Candidate ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Docking Studies ◽  
Indian Isolate ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Hla System ◽  
Peptide Binding Groove

Abstract The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about a million confirmed cases worldwide. Being an airborne infection, it can be highly fatal to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can acts act as an effective vaccine candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to studies to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as a vaccine candidate. The identified epitopes can be subjected to further studies for the development of SARS-CoV-2 vaccine.

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

2019 ◽  
Vol 73 (6) ◽  
pp. 318-321
Author(s):  
Zongjing Xie ◽  
Bingmei Wang ◽  
Yongjie Chai ◽  
Junyin Chen
Keyword(s):  
Gastric Cancer ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Meta Analysis ◽  
Interleukin 4 ◽  
East Asians ◽  
Mannose Binding ◽  
Binding Lectin ◽  
Positive Results ◽  
Review Manager

AimsAssociations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε−1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies.MethodsEligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies.ResultsForty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms.ConclusionCollectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.

scholarly journals Fusogenic Liposome can be Used as an Effective Vaccine Carrier for Peptide Vaccination to Induce Cytotoxic T Lymphocyte (CTL) Response

2005 ◽  
Vol 28 (1) ◽  
pp. 192-193 ◽  
Author(s):  
Toshiki Sugita ◽  
Tomoaki Yoshikawa ◽  
Jian-Qing Gao ◽  
Mariko Shimokawa ◽  
Atushi Oda ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Effective Vaccine ◽  
Peptide Vaccination ◽  
Ctl Response ◽  
Vaccine Carrier

scholarly journals The Cytotoxic T-Lymphocyte Epitope of the Plasmodium falciparum Circumsporozoite Protein Also Modulates the Efficiency of Receptor-Ligand Interaction with Hepatocytes

2000 ◽  
Vol 68 (2) ◽  
pp. 740-743 ◽  
Author(s):  
Dharmendar Rathore ◽  
Thomas F. McCutchan
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Liver Cells ◽  
Circumsporozoite Protein ◽  
Significant Implication ◽  
Host Liver ◽  
Ligand Interaction ◽  
Receptor Ligand ◽  
Host Immune Responses ◽  
Mosquito Salivary Gland

ABSTRACT Malaria sporozoites are transmitted from the mosquito salivary gland to host hepatocytes within minutes of an infectious bite. The circumsporozoite protein (CS), which covers the surface ofPlasmodium sporozoites, functions during these minutes in the targeting of host liver cells. The protein's potentially important role in an antimalaria vaccine has spawned interest in both the host immune responses to the parasite's presence and the actual functional role of the protein in the targeting of host liver cells. Here we show that the region of CS known to elicit a cytotoxic T-lymphocyte (CTL) response to irradiated sporozoites also, somewhat ironically, mediates the receptor-ligand interaction essential to parasite invasion of the host. Hence, the structure of CS represents a balance of potentially counterdirectional forces. Polymorphism in the CTL epitope appears to be a product of this balanced state as opposed to an “arms race” as it is so often portrayed. The conceptual difference between the theories regarding the maintainance of polymorphism in CTL epitopes may have significant implication for vaccine design.

scholarly journals Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Viswajit Mulpuru ◽  
Nidhi Mishra
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Docking Studies ◽  
Indian Isolate ◽  
Dynamics Simulation ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Hla System ◽  
Epitope Candidate

AbstractThe Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about thirty million confirmed cases worldwide as of September 2020. Being an airborne infection, it can be catastrophic to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can act as an effective vaccine epitope candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to be studied to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as an epitope candidate. The candidacy was further analyzed using sequence conservation studies and molecular dynamics simulation. The identified epitopes can be subjected to further studies for the development of the SARS-CoV-2 vaccine.

scholarly journals Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox

2001 ◽  
Vol 75 (3) ◽  
pp. 1205-1210 ◽  
Author(s):  
Ronald J. Jackson ◽  
Alistair J. Ramsay ◽  
Carina D. Christensen ◽  
Sandra Beaton ◽  
Diana F. Hall ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Genetic Resistance ◽  
Interleukin 4 ◽  
Immune Memory ◽  
Laboratory Mice ◽  
Ectromelia Virus ◽  
Lymphocyte Responses ◽  
Significant Mortality

ABSTRACT Genetic resistance to clinical mousepox (ectromelia virus) varies among inbred laboratory mice and is characterized by an effective natural killer (NK) response and the early onset of a strong CD8+ cytotoxic T-lymphocyte (CTL) response in resistant mice. We have investigated the influence of virus-expressed mouse interleukin-4 (IL-4) on the cell-mediated response during infection. It was observed that expression of IL-4 by a thymidine kinase-positive ectromelia virus suppressed cytolytic responses of NK and CTL and the expression of gamma interferon by the latter. Genetically resistant mice infected with the IL-4-expressing virus developed symptoms of acute mousepox accompanied by high mortality, similar to the disease seen when genetically sensitive mice are infected with the virulent Moscow strain. Strikingly, infection of recently immunized genetically resistant mice with the virus expressing IL-4 also resulted in significant mortality due to fulminant mousepox. These data therefore suggest that virus-encoded IL-4 not only suppresses primary antiviral cell-mediated immune responses but also can inhibit the expression of immune memory responses.

scholarly journals Induction of Immune Tolerance in Asthmatic Mice by Vaccination with DNA Encoding an Allergen–Cytotoxic T Lymphocyte-Associated Antigen 4 Combination

2011 ◽  
Vol 18 (5) ◽  
pp. 807-814 ◽  
Author(s):  
Fang Zhang ◽  
Gang Huang ◽  
Bo Hu ◽  
Yong Song ◽  
Yi Shi
Keyword(s):  
Airway Inflammation ◽  
Dna Vaccine ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Treg Cells ◽  
Airway Hyperreactivity ◽  
Interleukin 4 ◽  
High Dose ◽  
Dna Encoding ◽  
Allergen Specific Immunotherapy

ABSTRACTAllergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen–cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA3.1) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed and transfected into COS-7 cells to obtain the fusion protein OVA-CTLA-4, which was able to bind the B7 ligand on dendritic cells (DCs), and induced CD25+Foxp3+regulatory T (Treg) cells by the coculture of naive CD4+T cells with DCsin vitro. In an animal study, BALB/c mice were sensitized and challenged with OVA to establish the asthmatic model. Vaccination with a high dose of OVA-CTLA-4-pcDNA3.1significantly decreased interleukin-4 (IL-4) and IL-5 levels and eosinophil counts and prevented OVA-induced reduction of the gamma interferon level in the bronchoalveolar lavage fluid. In addition, these mice suffered less severe airway inflammation and had lower levels of OVA-specific IgE and IgG1 titers in serum. Also, high-dose OVA-CTLA-4-pcDNA3.1vaccination inhibited the development of airway hyperreactivity and prevented OVA-induced reduction of the percentages of Foxp3+Treg cells in the spleen. Our results indicate that a high dose of allergen-CTLA-4-encoding DNA vaccine was more effective in preventing an allergen-induced Th2-skewed immune response through the induction of Treg cells and may be a new alternative therapy for asthma.

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