Abstract The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about protective mechanisms underlying its efficiency. In this study, we analyzed relative contribution of cell-mediated and humoral immunity to vaccine-induced protection a murine model YF-17D infection. Using different strains knockout mice, found that CD4+ T cells, B Abs are required for full clinical vaccinated whereas CD8+ cells dispensable long-term survival after intracerebral...

Abstract Background This randomized, double‐blind trial was conducted to determine the optimal dose for clinical efficacy of SQ tree SLIT ‐tablet. An environmental exposure chamber ( EEC ) used reduce variability allergen and allow investigation symptom reduction towards different species from birch homologous group in separate sessions. Methods Eligible subjects (N = 219) were randomized receive treatment with placebo or ‐tablet (2, 7, 12 DU 24 weeks. pollen challenges outside season...

Purpose: Geographic atrophy (GA) secondary to age-related macular degeneration is a progressive retinal degenerative disease. Systemic chemokine receptors and known risk-associated single-nucleotide polymorphisms have been associated with GA pathogenesis. Because halting progression pivotal for patients, we investigated the association of candidate rate (PR) atrophic lesions in patients GA. Methods: This prospective observational study conducted at single center included 85 45 healthy...

Citrullination catalysed by peptidylarginine deiminases (PADs) plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and, possibly, several other inflammatory diseases. Non-physiological reducing agents such as dithiothreitol (DTT) are normally added to the reaction buffer when determining PAD activity vitro. We investigated ability of reduced glutathione (GSH), most abundant intracellular small-molecule thiol vivo, activate PADs....

The threat from unpredictable influenza virus pandemics necessitates the development of a new type vaccine. Since internal proteins are highly conserved, induction T cells targeting these antigens may provide solution. Indeed, adenoviral (Ad) vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. In this study we confirm that systemic (subcutaneous (s.c.) immunization rapidly induced heterosubtypic predominantly mediated by CD8 cells, but...

ABSTRACT It has been reported that adenovirus (Ad)-primed CD8 T cells may display a distinct and partially exhausted phenotype. Given the practical implications of this claim, we decided to analyze in detail quality Ad-primed by directly comparing these induced through infection with lymphocytic choriomeningitis virus (LCMV). We found localized immunization intermediate doses Ad vector induces moderate number functional which qualitatively match those LCMV-infected mice. The numbers be...

Abstract The use of replication-deficient adenoviruses as vehicles for transfer foreign genes offers many advantages in a vaccine setting, eliciting strong cellular immune responses involving both CD8+ and CD4+ T cells. Further improving the immunogenicity, tethering inserted target Ag to MHC class II–associated invariant chain (Ii) greatly enhances presentation most Ags, well overall protection against viral infection, such lymphocytic choriomeningitis virus (LCMV). present study extends...

Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability induce potent and protective CD8 T-cell responses. However, critical issue regarding the use of these is existence inhibitory immunity against most commonly used Ad5 vector in large part human population. We recently developed an improved adenoviral system which expresses transgene tethered MHC class II associated invariant chain (Ii). To further evaluate this system, concept pre-existing...

Abstract Recently, we showed that combined intranasal and subcutaneous immunization with a non-replicating adenoviral vector expressing NP of influenza A, strain PR8, induced long-standing protection against range A viruses. However, H-2 b mice challenged an mutated in the dominant 366 epitope were not efficiently protected. To address this problem, envision use cocktail adenovectors targeting different internal proteins virus. Consequently, investigated possibility using PB1 as target for...

Suppressors of cytokine signaling (SOCS) proteins are intracellular that inhibit in a variety cell types. A number viral infections have been associated with SOCS upregulation; however, not much is known about the mechanisms regulating expression during infection. In this study, we used two pathologically distinct intracerebral (i.c.) infection models to characterize temporal and spatial aspects virus-infected central nervous system (CNS), by employing various knockout mouse models, sought...

Abstract Adenoviral vectors have long been forerunners in the development of effective CD8 T cell–based vaccines; therefore, it is imperative that we understand factors controlling induction robust and long-lasting transgene-specific immune responses by these vectors. In this study, investigated organ sites, molecules, cell subsets play a critical role priming cells after vaccination with replication-deficient adenoviral vector. Using human adenovirus serotype 5 (Ad5) vector genetically...

Dysregulation of the complement system is involved in development age-related macular degeneration (AMD). The cascade regulated by membrane bound regulatory proteins (Cregs) on mononuclear leukocytes among others. This study aims to investigate systemic and Cregs AMD stages their association with treatment response neovascular (nAMD).

We have previously shown that for the majority of antigens, adenoviral vaccines expressing target antigen fused to MHC associated invariant chain (Ii) induce an accelerated, augmented, and prolonged transgene-specific CD8(+) T-cell response. Here we describe a new vaccine vector approach where Ii is expressed from E1 region IL-2 E3 region. Immunization mice with this construct resulted in augmented primary effector Furthermore, melanoma model observed significantly tumor control vaccinated...

Abstract As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future should preferentially target subdominant epitopes, idea being this allow greater breadth induced T cell response and, hence, efficiency controlling escape variants. However, to our knowledge evidence supporting concept is limited at best. To improve upon this, we used murine lymphocytic choriomeningitis virus model and adenoviral vectors...

During recent years, evidence has emerged that immune privileged sites such as the CNS and retina may be more integrated in systemic response to infection than was previously believed. In line with this, it recently shown a acute virus leads infiltration of CD8 T cells brains immunocompetent mice. this study, we extend these findings neurological tissue eye, namely retina. We show an mice transient cell is not directed by inside were found throughout retinal tissue, had high expression CXCR6...

Blindness or vision loss due to neuroretinal and photoreceptor degeneration affects millions of individuals worldwide. In numerous neurodegenerative diseases, including age-related macular degeneration, dysregulated immune response-mediated retinal has been found play a critical role in the disease pathogenesis. To better understand pathogenic mechanisms underlying we used mouse model systemic activation where infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13. Here,...

Aging changes the responsiveness of our immune defense, and this decline in reactivity plays an important role increased susceptibility to infections that marks progressing age. is also most pronounced risk factor for development age-related macular degeneration (AMD), a disease characterized by dysfunctional retinal pigment epithelial (RPE) cells loss central vision. We have previously shown acute systemic viral infection has large impact on retina young mice, leading upregulation...

Abstract Cytokines role in the adaptive immune system has drawn significantly attention recent years. An important finding is that T-cell quality and numbers tend to decline cancer patients, partly as a consequence of inadequate amounts cytokine interleukin-2 (IL-2), due general tumor environmental down regulation activating molecules CD80/86. Thus, co-administration cytokine(s), combination with an antigen interest, possesses potential modulate response favorable direction. As consequence,...

Abstract Current influenza vaccines are inducing antibody-mediated immunity toward the surface proteins hemagglutinin and neuraminidase. High variability of these results in costly annual evaluation production new vaccines, not providing protection against heterosubtypic or emerging pandemic strains. Consequently, there is a need for universal vaccine strategy. Unlike proteins, internal highly conserved. By vaccinating systemically locally with nucleoprotein encoded an adenovirus (AdNP) we...