Association of recombinant proteins rASP-2 and rTC24 from Trypanosoma cruzi as a vaccine strategy against Chagas disease induces a mixed Th1/ Th17 immune response.

How Viral Infections Cause Exacerbation of Airway Diseases

We have investigated the use of the graphical processing unit to accelerate the software package DarkSUSY. DarkSUSY is, among other things, used for calculating the dark matter relic density -- an measurable quantity -- given the supersymmetric neutralino, χ, as a dark matter candidate. Supersymmetric theories have many free parameters and we want to calculate the relic density for large areas of the parameter space. The results can then be compared with observations and to constrain the parameters. A faster DarkSUSY would allow for larger searches in the parameter space. We modified DarkSUSY using Nvidia's CUDA platform and wrote a program that, by using the GPU, calculates the χ + χ <-> W+ + W- contribution to the annihilation cross-section. Our initial try was only negligible faster than our non-CUDA program due to under-utilization of the GPU, but solving that the program was 47 times faster than the reference program. We also report on difficulties we faced, both solved and unsolved so the reader can make an informed decision on the worth of rewriting so that the heavy calculations in DarkSUSY use the GPU.

Longevity and Clinical Effectiveness of the Humoral and Cellular Responses to SARS-CoV-2 Vaccination in Hemodialysis Patients

Norovirus (NoV) virus-like particles (VLPs) adjuvanted with aluminum hydroxide (Alum) are common vaccine candidates in clinical studies. Alum adjuvants usually inefficiently assist recombinant proteins to induce cellular immune responses. Thus, novel adjuvants are required to develop NoV vaccines that could induce both efficient humoral and robust cellular immune responses. Lipid nanoparticles (LNPs) are well-known mRNA delivery vehicles. Increasing evidence suggests that LNPs may have intrinsic adjuvant activity and can be used as adjuvants for recombinant protein vaccines; however, the underlying mechanism remains poorly understood. In this study, we compared the adjuvant effect of LNPs and Alum for a bivalent GI.1/GII.4 NoV VLP vaccine. Compared with Alum, LNP-adjuvanted vaccines induced earlier production of binding, blocking, and neutralizing antibodies and promoted a more balanced IgG2a/IgG1 ratio. It is crucial that LNP-adjuvanted vaccines induced stronger Th1-type cytokine-producing CD4+ T cell and CD8+ T cell responses than Alum. The adjuvant activity of LNPs depended on the ionizable lipid components. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor (TLR) 9, thus affecting the adaptive immune responses of the vaccine. This conclusion was supported by RNA-seq analysis and in vitro cell experiments and by the deeply blunted T cell responses in IFNαR1-/- mice immunized with LNP-adjuvanted vaccines. This study not only identified LNPs as a high quality adjuvant for NoV VLP vaccines, but also clarified the underlying mechanism of LNPs as a potent immunostimulatory component for improving protein subunit vaccines.IMPORTANCEWith the rapid development of mRNA vaccines, recurrent studies show that lipid nanoparticles (LNPs) have adjuvant activity. However, the mechanism of its adjuvant effect in protein vaccines remains unknown. In this study, we found that the LNP-adjuvanted norovirus bivalent virus-like particle vaccines led to durable antibody responses as well as Th1-type cytokine-producing CD4+ T cell and CD8+ T cell responses, which exceeded the efficiency of the conventional adjuvant aluminum hydroxide. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor 9, thus affecting the adaptive immune responses of the vaccine. This work unveils that LNPs as a potent immunostimulatory component may be ideal for generating CD8+ T cell and B cell responses for recombinant protein vaccines.

Who benefits from cellular immune response during the Chagas disease?

A Functional Polymorphism of Toll-Like Receptor 4 Gene Increases Risk of Gastric Carcinoma and Its Precursors

Spleen-selective co-delivery of mRNA and TLR4 agonist-loaded LNPs for synergistic immunostimulation and Th1 immune responses

Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis

Towards addressing questions related to HIV pathogenesis and vaccine design we are fortunate to have the availability of the SIV-infected rhesus macaque model. The strengths of this model which include a rapid rate of progression to AIDS and knowledge of the dose route and strain of the infecting virus complement studies in HIV-infected patients in which the reagents host genetics and access to samples are more extensive and better defined. Unfortunately there is currently still too little known about the antiviral immune responses in either system to directly and accurately compare their similarities and differences and to draw any definitive conclusions. Therefore the data and views presented herein will simply reflect what has recently been discovered in both humans and non-human primate studies. (excerpt)

Toll-like Receptor 9 Triggers an Innate Immune Response to Helper-dependent Adenoviral Vectors

DNA Vaccination and All-Trans Retinoic Acid Treatment-Induced Long Term Survival Requires CD4+ and CD8+ T-Cell Activation in An APL Mouse Model.

Retroviral Vectors Induce Epigenetic Chromatin Modifications and IL-10 Production in Transduced B Cells via Activation of Toll-like Receptor 2

EDITORIAL article Front. Immunol., 02 April 2015Sec. Immunological Tolerance and Regulation Volume 6 - 2015 | https://doi.org/10.3389/fimmu.2015.00146

This paper presents a study of the flow of ice in wedge-shaped converging channels. Such flows are encountered in the relatively constricted waters of the Canadian Arctic Archipelago. Ridging, lead opening patterns, development of a highpressure area, and arch formation are some of the processes which take place during ice flow through converging channels. An idealized geometry and steady wind forcing were used in the testing. The results give ice cover velocity, distribution of stresses, ice thickness, area coverage and ridging. Some of the conditions leading to arch formation at the constricted exit of the channel are explored.

Rethinking hepatitis C viral kinetics: Insights into host-virus interactions in ‘difficult-to-treat’ groups and implications for novel treatment approaches