scholarly journals Immunological Cross-Reactivity of an Ancestral and the Most Recent Pandemic Norovirus GII.4 Variant

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 91 ◽  
Author(s):  
Kirsi Tamminen ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Antigenic Variation ◽  
Neutralization Assay ◽  
Cross Reactivity ◽  
High Avidity ◽  
Virus Like Particle ◽  
Blocking Activity ◽  
Ifn Γ ◽  
Pandemic Strains ◽  
Norovirus Gii ◽  
Antigen Presenting

Norovirus (NoV) genotype GII.4 is responsible for the majority of NoV infections causing pandemics every few years. A NoV virus-like particle (VLP)-based vaccine should optimally cover the high antigenic variation within the GII.4 genotype. We compared the immune responses generated by VLPs of the ancestral GII.4 1999 strain (GII.4 1995/96 US variant) and the most recent GII.4 Sydney 2012 pandemic strains in mice. No significant differences were observed in the type-specific responses but GII.4 1999 VLPs were more potent in inducing high-avidity antibodies with better cross-reactivity. GII.4 1999 immune sera blocked binding of GII.4 2006 and GII.4 2012 VLPs to the putative receptors in a surrogate neutralization assay, whereas GII.4 2012 immune sera only had low blocking activity against GII.4 2006 VLPs. Amino acid substitution in the NERK motif (amino acids 310, 316, 484, and 493, respectively), altering the access to conserved blocking epitope F, moderately improved the cross-blocking responses against mutated GII.4 2012 VLPs (D310N). NoV GII.4 1999 VLPs, uptaken and processed by antigen-presenting cells, induced stronger interferon gamma (IFN-γ) production from mice splenocytes than GII.4 2012 VLPs. These results support the use of GII.4 1999 VLPs as a major component of a NoV vaccine.

scholarly journals Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Kirsi Tamminen ◽  
Suvi Heinimäki ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Adjuvant Effect ◽  
Particle Uptake ◽  
Virus Like Particle ◽  
Norovirus Gii ◽  
Immortalized Cell ◽  
Antigen Presenting

We have previously shown that rotavirus (RV) inner capsid protein VP6 has an adjuvant effect on norovirus (NoV) virus-like particle- (VLP-) induced immune responses and studied the adjuvant mechanism in immortalized cell lines used as antigen-presenting cells (APCs). Here, we investigated the uptake and presentation of RV VP6 and NoV GII.4 VLPs by primary bone marrow-derived dendritic cells (BMDCs). The adjuvant effect of VP6 on GII.4 VLP presentation and NoV-specific immune response induction by BMDC in vivo was also studied. Intracellular staining demonstrated that BMDCs internalized both antigens, but VP6 more efficiently than NoV VLPs. Both antigens were processed and presented to antigen-primed T cells, which responded by robust interferon γ secretion. When GII.4 VLPs and VP6 were mixed in the same pulsing reaction, a subpopulation of the cells had uptaken both antigens. Furthermore, VP6 copulsing increased GII.4 VLP uptake by 37% and activated BMDCs to secrete 2-5-fold increased levels of interleukin 6 and tumor necrosis factor α compared to VLP pulsing alone. When in vitro-pulsed BMDCs were transferred to syngeneic BALB/c mice, VP6 improved NoV-specific antibody responses. The results of this study support the earlier findings of VP6 adjuvant effect in vitro and in vivo.

scholarly journals Durability and Cross-Reactivity of Immune Responses Induced by an AS03 Adjuvanted Plant-Based Recombinant Virus-Like Particle Vaccine for COVID-19

2021 ◽  
Author(s):  
Philipe A.M. Gobeil ◽  
Stéphane Pillet ◽  
Iohann Boulay ◽  
Nathalie Charland ◽  
Aurélien Lorin ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Phase 1 ◽  
Cross Reactivity ◽  
Interleukin 4 ◽  
Phase 3 ◽  
Live Virus ◽  
Post Vaccination ◽  
Virus Like Particle ◽  
Ifn Γ ◽  
Alpha Variant

As the SARS-COV-2 pandemic evolves, what is expected of vaccines extends beyond efficacy and includes evaluations of both durability and cross-reactivity to emerging variants. To complement an on-going Phase 3 efficacy study, this report expands on previously reported immunogenicity results from a Phase 1 trial of an AS03-adjuvanted, plant-based virus-like particle (VLP) displaying the spike glycoprotein of the Wuhan strain of SARS-CoV-2 virus (NCT04450004). Durability of the humoral and cellular responses against the ancestral strain was evaluated 6 months post-second dose (Day 201) at which time ~94% of vaccinated individuals remained seropositive. Interferon gamma (IFN-γ) and interleukin 4 (IL-4) responses remained detectable in ~94% and ~92% of vaccinated individuals respectively. Cross-reactivity of neutralizing antibodies to Alpha (B.1.17), Beta (B.1.351), and Gamma (P.1) variants of concern (VOC) were also measured. Twenty-one days after the second vaccination, detectable neutralizing antibodies were observed to the Alpha variant by both pseudovirion and wild-type assays for all vaccinated individuals, while 94.7% of individuals had detectable antibodies to the Beta variant in both assays. Neutralizing antibodies to the Gamma variant were detected in 100% and 94.7% of individuals using the pseudovirion and live virus neutralization assays, respectively. In all cases, the vaccine-induced neutralizing GMTs to the VOC 3 weeks post-vaccination were greater than the Wuhan-specific neutralization titers seen in individuals recovered from COVID-19.

scholarly journals Low‐affinity but high‐avidity interactions may offer an explanation forIgE‐mediated allergen‐cross‐reactivity

Allergy ◽  
2021 ◽  
Author(s):  
Xinyue Chang ◽  
Lisha Zha ◽  
Alexandra Wallimann ◽  
Mona O. Mohsen ◽  
Pascal Krenger ◽  
...  
Keyword(s):  
Cross Reactivity ◽  
High Avidity

scholarly journals Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 312
Author(s):  
Eva Wagner-Drouet ◽  
Daniel Teschner ◽  
Christine Wolschke ◽  
Kerstin Schäfer-Eckart ◽  
Johannes Gärtner ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Response ◽  
Elispot Assay ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Ifn Γ ◽  
Antigen Presenting

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8+ counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients.

scholarly journals Differential Regulation of Cathepsin S and Cathepsin L in Interferon γ–treated Macrophages

2003 ◽  
Vol 197 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Courtney Beers ◽  
Karen Honey ◽  
Susan Fink ◽  
Katherine Forbush ◽  
Alexander Rudensky
Keyword(s):  
Cathepsin L ◽  
Specific Inhibitor ◽  
Cell Types ◽  
Interferon Γ ◽  
Cathepsin S ◽  
Antigen Presenting Cell ◽  
Relative Contribution ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Antigen Presenting

Cathepsin S (catS) and cathepsin L (catL) mediate late stages of invariant chain (Ii) degradation in discrete antigen-presenting cell types. Macrophages (Mϕs) are unique in that they express both proteases and here we sought to determine the relative contribution of each enzyme. We observe that catL plays no significant role in Ii cleavage in interferon (IFN)-γ–stimulated Mϕs. In addition, our studies show that the level of catL activity is significantly decreased in Mϕs cultured in the presence of IFN-γ whereas catS activity increases. The decrease in catL activity upon cytokine treatment occurs despite the persistence of high levels of mature catL protein, suggesting that a specific inhibitor of the enzyme is up-regulated in IFN-γ–stimulated peritoneal Mϕs. Similar inhibition of activity is observed in dendritic cells engineered to overexpress catL. Such enzymatic inhibition in Mϕs exhibits only partial dependence upon Ii and therefore, other mechanisms of catL inhibition are regulated by IFN-γ. Thus, during a T helper cell type 1 immune response catL inhibition in Mϕs results in preferential usage of catS, such that major histocompatibility complex class II presentation by all bone marrow–derived antigen-presenting cell is regulated by catS.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

scholarly journals Natural Killer Dendritic Cells Have Both Antigen Presenting and Lytic Function and in Response to CpG Produce IFN-γ via Autocrine IL-12

2005 ◽  
Vol 174 (5) ◽  
pp. 2612-2618 ◽  
Author(s):  
Venu G. Pillarisetty ◽  
Steven C. Katz ◽  
Joshua I. Bleier ◽  
Alaap B. Shah ◽  
Ronald P. DeMatteo
Keyword(s):  
Dendritic Cells ◽  
Natural Killer ◽  
Lytic Function ◽  
Ifn Γ ◽  
Antigen Presenting

Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding

2016 ◽  
Vol 29 (5) ◽  
pp. 315-319 ◽  
Author(s):  
Kirsi Tamminen ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Receptor Binding ◽  
Virus Like Particle ◽  
Norovirus Gii

scholarly journals Differential Deactivation of Human Dendritic Cells by Endotoxin Desensitization: Role of Tumor Necrosis Factor-α and Prostaglandin E2

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3112-3117 ◽  
Author(s):  
Claudia Rieser ◽  
Christine Papesh ◽  
Manfred Herold ◽  
Günther Böck ◽  
Reinhold Ramoner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Prostaglandin E2 ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mixed Leukocyte Reaction ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Antigen Presenting ◽  
Necrosis Factor

The endotoxin (lipopolysaccharide)-induced cytokine response is followed by a state of unresponsiveness to lipopolysaccharide (LPS) referred to as LPS tolerance or endotoxin desensitization. LPS tolerance, which can be experimentally induced in vitro and in vivo, is also known to occur in septic disease. Here, we evaluated whether dendritic cells (DC), the most potent antigen-presenting cells, are also subject to this phenomenon. Single doses of LPS added at the initiation of DC culture inhibited in a dose-dependent fashion the production of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-12, but not the production of IL-8, in response to a second LPS challenge in day-5 DC. In addition, the LPS-induced expression of the CD83 maturation antigen was inhibited in these cells. Moreover, the endocytic activity of DC generated in the presence of LPS was dramatically reduced. DC desensitized with LPS were potent stimulators of T-cell proliferation but poor inducers of interferon-γ (IFN-γ) production in the allogeneic mixed leukocyte reaction. TNF-α and prostaglandin E2, two major products of LPS stimulation, could replace LPS for the induction of tolerance to LPS. Moreover, treatment of desensitized DC with TNF-α plus prostaglandin E2 fully restored CD83 expression and partially restored IL-12 production as well as the IFN-γ–inducing activity of DC in the mixed leukocyte reaction. Our data show that human DC are highly susceptible to the induction of LPS tolerance, which seems to be a state of differential deactivation in which some functions are impaired whereas others are retained. Tolerization at the level of the professional antigen-presenting cell by inflammatory mediators may play an important role in septic disease and in the origin of cancers associated with chronic inflammation.

New Generation Vaccines for COVID-19 Based on Peptide, Viral Vector, Artificial Antigen Presenting Cell, DNA or mRNA

2022 ◽  
Author(s):  
Marzieh Rezaei ◽  
Mahboobeh Nazari
Keyword(s):  
Infectious Disease ◽  
Viral Vector ◽  
Google Scholar ◽  
Cochrane Library ◽  
Protein Subunit ◽  
Virus Like Particle ◽  
Artificial Antigen ◽  
Attenuated Virus ◽  
Antigen Presenting ◽  
New Generation

At present, effective vaccines have been developed as the most successful approaches for preventing widespread infectious disease. The global efforts are focusing with the aim of eliminating and overcoming the Coronavirus Disease 2019 (COVID-19) and are developing vaccines from the date it was announced as a pandemic disease. In this study, PubMed, Embase, Cochrane Library, Clinicaltrial.gov, WHO reports, Science Direct, Scopus, Google Scholar, and Springer databases were searched for finding the relevant studies about the COVID-19 vaccines. This article provides an overview of multiple vaccines that have been manufactured from December 2020 up to April 2021 and also offers a perspective on their efficacy, safety, advantages, and limitations. Currently, there are several categories of COVID-19 vaccines based on Protein Subunit (PS), Inactivated Virus (IV), Virus Like Particle (VLP), Live Attenuated Virus (LAV), Viral Vector (replicating) (VVr) and Viral Vector (non-replicating) (VVnr) in progress or finalized as indicated by the WHO reporting of April 1, 2020.

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