SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells, and their function is essential to configure adaptative immunity and avoid excessive inflammation. DCs are predicted to play a crucial role in the clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell receptor binding and subsequent fusion of the viral particle with host cell, is a key step to induce effective immunity against this virus and in the S protein-based vaccination protocols.

Type I Interferon acts as a major barrier to the establishment of infectious bursal disease virus (IBDV) persistent infections.

Infectious bursal disease virus (IBDV), the best characterized member of the family, is a highly relevant avian pathogen causing both acute and persistent infections in different avian hosts. Here, we describe the establishment of clonal, long-term, productive persistent IBDV infections in DF-1 chicken embryonic fibroblasts. Although virus yields in persistently-infected cells are exceedingly lower than those detected in acutely infected cells, the replication fitness of viruses isolated from persistently-infected cells is higher than that of the parental virus.

Activation of the autophagy pathway by Torovirus infection is irrelevant for virus replication.

Autophagy is a conserved eukaryotic process that mediates lysosomal degradation of cytoplasmic macromolecules and damaged organelles, also exerting an important role in the elimination of intracellular pathogens. Despite the antiviral role of autophagy, many studies suggest that some positive-stranded RNA viruses exploit this pathway to facilitate their own replication. In this study, we demonstrate that the equine torovirus Berne virus (BEV), the prototype member of the Torovirus genus (Coronaviridae Family, Nidovirales Order), induces autophagy at late times post-infection.

TETIS study: evaluation of new topical hemostatic agent TT-173 in tooth extraction.

Objectives: TT-173 is a new hemostatic agent consisting of yeast-derived microvesicles containing a modified version of recombinant human tissue factor. In the present work, the procoagulant activity of TT-173 has been evaluated for the first time in humans.

Methods: This is a phase I, randomized, placebo-controlled study to evaluate the efficacy, safety, systemic absorption, and immunogenicity of TT-173 in healthy volunteers undergoing tooth extraction.

Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8(+) T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+) T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein.

Improving recombinant MVA immune responses: potentiation of the immune responses to HIV-1 with MVA and DNA vectors expressing Env and the cytokines IL-12 and IFN-gamma.

Recombinants based on vaccinia virus vectors, especially on the highly attenuated modified vaccinia virus Ankara (MVA) strain, are now being tested in clinical trials for safety and immunogenicity, using prime/boost heterologous regimes of vaccination. Due to the limited replication capacity of MVA, it is necessary to develop procedures that can enhance the specific cellular immune responses to the recombinant antigen delivered by the MVA vector. In this investigation, we have characterized the systemic immune responses in BALB/c mice using interferon-gamma (IFN-gamma) or interleukin-12 (IL-12) in an adjuvant-like manner elicited by MVA recombinants or naked DNA vectors expressing one of those cytokines in combination with the human immunodeficiency virus type 1 (HIV-1) envelope (Env) as antigen.

Mucosal immunization of sheep with a Maedi-Visna virus (MVV) env DNA vaccine protects against early MVV productive infection.

Gene gun mucosal DNA immunization of sheep with a plasmid expressing the env gene of Maedi-Visna virus (MVV) was used to examine the protection against MVV infection in sheep from a naturally infected flock. For immunization, sheep were primed with a pcDNA plasmid (pcDNA-env) encoding the Env glycoproteins of MVV and boosted with combined pcDNA-env and pCR3.1-IFN-gamma plasmid inoculations.

Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo.

There is mounting evidence that the established paradigm of nitric oxide (NO) biochemistry, from formation through NO synthases, over interaction with soluble guanylyl cyclase, to eventual disposal as nitrite/nitrate, represents only part of a richer chemistry through which NO elicits biological signaling. Additional pathways have been suggested that include interaction of NO-derived metabolites with thiols and metals to form S-nitrosothiols (RSNOs) and metal nitrosyls. Despite the overwhelming attention paid in this regard to RSNOs, little is known about the stability of these species, their significance outside the circulation, and whether other nitros(yl)ation products are of equal importance.

Induction of protective immunity against malaria by priming-boosting immunization with recombinant cold-adapted influenza and modified vaccinia Ankara viruses expressing a CD8+-T-cell epitope derived from the circumsporozoite protein of Plasmodium yoelii.

We immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus Ankara), both expressing a CD8(+)-T-cell epitope derived from malaria sporozoites. This vaccination regimen elicited high levels of protection against malaria. This is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated.

Protection in dogs against visceral leishmaniasis caused by Leishmania infantum is achieved by immunization with a heterologous prime-boost regime using DNA and vaccinia recombinant vectors expressing LACK.

A heterologous prime-boost vaccination regime with DNA and recombinant vaccinia virus (rVV) vectors expressing relevant antigens has been shown to enhance specific cellular immune responses and to elicit protection against a variety of pathogens in animal models. In this paper, we describe the effectiveness of the prime-boost strategy by immunizing dogs with a plasmid carrying the gene for the LACK antigen from Leishmania infantum (DNA-LACK) followed by a booster with a rVV containing the same gene (rVV-LACK). Thereafter, animals were challenged with L.

A heterologous prime-boost regime using DNA and recombinant vaccinia virus expressing the Leishmania infantum P36/LACK antigen protects BALB/c mice from cutaneous leishmaniasis.

A heterologous prime-boost vaccination with DNA vectors and vaccinia virus recombinants (VVr) has been shown to enhance specific cellular immune responses and to elicit significant protection against pathogens in animal models. In this study, we have analyzed, in the leishmaniasis cutaneous murine model, the effectiveness of this prime-boost strategy by immunizing with a DNA vector followed by boost with a VVr expressing the same Leishmania infantum P36/LACK antigen. After DNA priming and VVr boost, we challenged susceptible BALB/c mice with live L.

Endoplasmic reticulum-Golgi intermediate compartment membranes and vimentin filaments participate in vaccinia virus assembly.

Vaccinia virus (VV) has a complex morphogenetic pathway whose first steps are poorly characterized. We have studied the early phase of VV assembly, when viral factories and spherical immature viruses (IVs) form in the cytoplasm of the infected cell. After freeze-substitution numerous cellular elements are detected around assembling viruses: membranes, ribosomes, microtubules, filaments, and unidentified structures.