scholarly journals A NOVEL MULTI-EPITOPE PEPTIDE VACCINE CONSTRUCT AGAINST INFLUENZA A VIRUS AND STREPTOCOCCUS PNEUMONIAE CO-INFECTION: AN IN SILICO APPROACH

2020 ◽  
Vol 4 (2) ◽  
pp. 30-50
Author(s):  
Maha Kaiser ◽  
Amjad Ali
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Streptococcus Pneumoniae ◽  
Influenza A Virus ◽  
In Silico ◽  
Influenza A ◽  
Peptide Vaccine ◽  
Epitope Peptide ◽  
Ncbi Accession ◽  
Recognition Receptor

Viral and bacterial respiratory tract co-infections in the same host often result in severity and heightened pathology of illness compared to single infections. This has proven to be true for combined infections with Influenza A virus and the bacterium Streptococcus pneumoniae. Separate vaccines do exist for each individual infection but they prove to be ineffective and non-specific when the infection has multiplied in case of co-infection. The study utilised in silico approaches and proposed a structural design for multi-epitope peptide vaccine having the ability to target co-infection caused by A/New York/392/2004 (H3N2) and R6 strains of Influenza A virus (NCBI Accession: PRJNA15622) and Streptococcus pneumoniae (NCBI Accession: PRJNA278), respectively. Epitope prediction followed by protein prioritization was performed using the reference sequence of each strain to short list the epitopes that can later be used for constructing multi-epitope structure. The multi-epitope constructs having Cholera Toxin Subunit B as adjuvant and (Gly4Ser)3 as flexible linker were then analyzed for their ability to induce an effective immune response in human body for which Macrophage receptor with collagenous structure, Toll-like receptor 2, 4 and 5 were taken as Pattern Recognition Receptors. The significant immune response generated through each Pattern Recognition Receptor helped to conclude that multi-epitope peptide structures can be used as probable candidates for the design of vaccine. The combination of the epitopes LWSYNAELL and FTGKQLQVG of Influenza A virus and Streptococcus pneumoniae, respectively, induced highly significant immune response in case of each Pattern Recognition Receptor when tested through in-silico predictive tools.

scholarly journals Toll-Like Receptor 3/TRIF-Dependent IL-12p70 Secretion Mediated byStreptococcus pneumoniaeRNA and Its Priming by Influenza A Virus Coinfection in Human Dendritic Cells

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Laura Spelmink ◽  
Vicky Sender ◽  
Karina Hentrich ◽  
Thomas Kuri ◽  
Laura Plant ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Streptococcus Pneumoniae ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Monocyte ◽  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Pneumococcal Infections ◽  
Adaptor Molecule

ABSTRACTA functional immune response is crucial to prevent and limit infections withStreptococcus pneumoniae. Dendritic cells (DCs) play a central role in orchestrating the adaptive and innate immune responses by communicating with other cell types via antigen presentation and secretion of cytokines. In this study, we set out to understand how pneumococci activate human monocyte-derived DCs to produce interleukin-12 (IL-12) p70, an important cytokine during pneumococcal infections. We show that IL-12p70 production requires uptake of bacteria as well as the presence of the adaptor molecule TRIF, which is known to transfer signals of Toll-like receptor 3 (TLR3) or TLR4 from the endosome into the cell. While TLR4 is redundant for IL-12p70 production in DCs, we found that TLR3 is required to induce full IL-12p70 secretion. Influenza A virus (IAV) infection of DCs did not induce IL-12p70 but markedly upregulated TLR3 expression that during coinfection withS. pneumoniaesignificantly enhanced IL-12p70 secretion. Finally, we show that pneumococcal RNA can act as a bacterial stimulus for TLR3 and that it is a key signal to induce IL-12p70 production during challenge of DCs with pneumococci.IMPORTANCEStreptococcus pneumoniae, a common colonizer of the nose, is the causative agent of severe and deadly diseases. A well-orchestrated immune response is vital to prevent and limit these diseases. Dendritic cells (DCs) reside in the mucosal linings of the lungs and sample antigens. They are activated by pathogens to present antigens and secrete cytokines. While many studies focus on murine models, we focused our work on human monocyte-derived DCs. We found that pneumococcal RNA is an important stimulus in DCs to activate the endosomal receptor TLR3, a receptor previously not identified to sense pneumococci, and its adaptor molecule TRIF. This leads to secretion of the cytokine interleukin-12 (IL-12). Severe pneumococcal pneumonia occurs closely after influenza A virus (IAV) infection. We show that IAV infection upregulates TLR3 in DCs, which sensitizes the cells to endosomal pneumococcal RNA. This new insight contributes to unlock the interplay between pneumococci, IAV, and humans.

scholarly journals Pattern recognition receptor mediated downregulation of microRNA-650 fine-tunes MxA expression in dendritic cells infected with influenza A virus

2015 ◽  
Vol 46 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Tica Pichulik ◽  
Elham Khatamzas ◽  
Xiao Liu ◽  
Oliver Brain ◽  
Magno Delmiro Garcia ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Dendritic Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Pattern Recognition Receptor ◽  
Recognition Receptor

scholarly journals Peptidomimetic 1-Benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one Showed Cardioprotection Effect in a Myocardial Ischemia (MI) Mouse Model

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 72
Author(s):  
Lena Trifonov ◽  
Vadim Nudelman ◽  
Michael Zhenin ◽  
Guy Cohen ◽  
Krzysztof Jozwiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Myocardial Ischemia ◽  
Mouse Model ◽  
Innate Immune Response ◽  
Pattern Recognition Receptor ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Toll Like Receptors ◽  
Recognition Receptor

TLR4, a member of the toll-like receptors (TLRs) family, serves as a pattern recognition receptor in the innate immune response to different microbial pathogens. [...]

Influenza A virus facilitates Streptococcus pneumoniae transmission and disease

2010 ◽  
Vol 24 (6) ◽  
pp. 1789-1798 ◽  
Author(s):  
Dimitri A. Diavatopoulos ◽  
Kirsty R. Short ◽  
John T. Price ◽  
Jonathan J. Wilksch ◽  
Lorena E. Brown ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Influenza A Virus ◽  
Influenza A

scholarly journals Links between fecal microbiota and the response to vaccination against influenza A virus in pigs

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Marion Borey ◽  
Fany Blanc ◽  
Gaëtan Lemonnier ◽  
Jean-Jacques Leplat ◽  
Deborah Jardet ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Influenza A ◽  
16S Rrna Gene Sequencing ◽  
Serum Levels ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Vaccine Response ◽  
Specific Igg ◽  
Rrna Gene Sequencing

AbstractThis study describes the associations between fecal microbiota and vaccine response variability in pigs, using 98 piglets vaccinated against the influenza A virus at 28 days of age (D28) with a booster at D49. Immune response to the vaccine is measured at D49, D56, D63, and D146 by serum levels of IAV-specific IgG and assays of hemagglutination inhibition (HAI). Analysis of the pre-vaccination microbiota characterized by 16S rRNA gene sequencing of fecal DNA reveals a higher vaccine response in piglets with a richer microbiota, and shows that 23 operational taxonomic units (OTUs) are differentially abundant between high and low IAV-specific IgG producers at D63. A stronger immune response is linked with OTUs assigned to the genus Prevotella and family Muribaculaceae, and a weaker response is linked with OTUs assigned to the genera Helicobacter and Escherichia-Shigella. A set of 81 OTUs accurately predicts IAV-specific IgG and HAI titer levels at all time points, highlighting early and late associations between pre-vaccination fecal microbiota composition and immune response to the vaccine.

scholarly journals Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

2016 ◽  
Vol 85 (2) ◽  
Author(s):  
M. Nadeem Khan ◽  
Qingfu Xu ◽  
Michael E. Pichichero
Keyword(s):  
T Cells ◽  
Streptococcus Pneumoniae ◽  
Influenza A Virus ◽  
Influenza A ◽  
Passive Transfer ◽  
Bacterial Density ◽  
Content Type ◽  
Adult Mice ◽  
Significant Difference ◽  
Colonization Density

ABSTRACTAn increase inStreptococcus pneumoniaenasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic naturalS. pneumoniaepathogenesis, we commensally colonized the NPs of adult C57BL/6 mice withS. pneumoniaeserotype (ST) 6A or 8 and then coinfected them with mouse-adapted H1N1 influenza A virus (PR/8/34).S. pneumoniaeestablished effective commensal colonization, and influenza virus coinfection causedS. pneumoniaeNP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), anS. pneumoniaeadhesin vaccine candidate, for its ability to prevent invasiveS. pneumoniaedisease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction ofS. pneumoniaeNP density (>2.5 log units) than PhtD vaccination (∼1-log-unit reduction). However, no significant difference was observed with regard to the prevention ofS. pneumoniaebacteremia, and there was no difference in mortality. Depletion of CD4+T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4+T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4+T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasiveS. pneumoniaepathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals The pneumococcal two-component system VisRH is linked to enhanced intracellular survival of Streptococcus pneumoniae in influenza-infected pneumocytes

2019 ◽  
Author(s):  
Nicolás M. Reinoso-Vizcaíno ◽  
Melina B. Cian ◽  
Paulo R. Cortes ◽  
Nadia B. Olivero ◽  
Mirelys Hernandez-Morfa ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Stress Response ◽  
Influenza A Virus ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Intracellular Survival ◽  
Bacterial Pathogenesis ◽  
Two Component System ◽  
Component System ◽  
Two Component

AbstractThe virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system VisRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔvisR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔvisR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the VisRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.Author summaryS. pneumoniae is an inhabitant of the human nasopharynx that is capable of causing a variety of infections contributing to an estimated 1.6 million deaths each year. Many of these deaths occur as result of secondary S. pneumoniae infections following seasonal or pandemic influenza. Although S. pneumoniae is considered a typical extracellular pathogen, an intracellular survival mechanism has been more recently recognized as significant in bacterial pathogenesis. The synergistic effects between influenza A and S. pneumoniae in secondary bacterial infection are well documented; however, the effects of influenza infections on intracellular survival of S. pneumoniae are ill-defined. Here, we provide evidence that influenza infection increases S. pneumoniae intracellular survival in pneumocytes. We demonstrate that the poorly understood VisRH signal transduction system in pneumococcus controls the expression of genes involved in the stress response that S. pneumoniae needs to increase intracellular survival in influenza A-infected pneumocytes. These findings have important implications for understanding secondary bacterial pathogenesis following influenza and for the treatment of such infections in influenza-stricken patients.

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