A split influenza vaccine formulated with a combination adjuvant composed of alpha-D-glucan nanoparticles and a STING agonist elicits cross-protective immunity in pigs.

BACKGROUND: Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus. RESULTS: Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10+ myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ+ effector memory T-helper/memory cells, IL-17A+ total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A+ total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A+ T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ+ late effector CTLs and effector memory T-helper/memory cells, IL-17A+ total CTLs, late effector CTLs, and CXCL10+ myeloid cells in blood, as well as lung CXCL10+ plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs. CONCLUSIONS: Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.

Short Communication Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: results of a long-term follow-up of Brazilian siblings.

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive multisystem lysosomal storage disorder, which is characterized by the deficiency of the enzyme arylsulfatase B encoded by the ARSB gene. Treatment of this disease with enzyme-replacement therapy (ERT) improves the clinical status of and generates hope for MPS VI patients. However, only few reports on patients with MPS VI treated before 5 years of age have been published. Thus, the objective of this study was to compare the clinical parameters of two sisters affected by MPS VI who started ERT at different ages (9 years and 1 year 5 months, respectively) and to determine the most relevant clinical impacts of early treatment after 85 months of evaluation. The treatment was well tolerated by both siblings. ERT in the younger sibling resulted in increased growth, an improved 6-minute walk test, less coarse face, slower progression of cardiac valve disease, and the absence of compressive myelopathy compared to that in her older sister. On the other hand, the older sibling had typical MPS VI phenotypic features before the commencement of ERT. Corneal clouding, clawed hands, and progressive skeletal changes were observed in both siblings despite the treatment. Both siblings displayed reduced frequencies of upper respiratory infections and apnea indices. This study emphasizes that early diagnosis and treatment of MPS VI are critical for a better disease outcome and to enhance the quality of life for these patients.

Characterization of a novel functional porcine CD3+CD4lowCD8α+CD8ß+ T-helper/memory lymphocyte subset in the respiratory tract lymphoid tissues of swine influenza A virus vaccinated pigs.

The pig is emerging as a physiologically relevant biomedical large animal model. Delineating the functional roles of porcine adaptive T-lymphocyte subsets in health and disease is of critical significance, which facilitates mechanistic understanding of antigen-specific immune memory responses. We identified a novel T-helper/memory lymphocyte subset in pigs and performed phenotypic and functional characterization of these cells under steady state and following vaccination and infection with swine influenza A virus (SwIAV). A novel subset of CD3+CD4lowCD8α+CD8ß+ memory T-helper cells was identified in the blood of healthy adult pigs under homeostatic conditions. To understand the possible functional role/s of these cells, we characterized the antigen-specific T cell memory responses by multi-color flow cytometry in pigs vaccinated with a whole inactivated SwIAV vaccine, formulated with a phytoglycogen nanoparticle/STING agonist (ADU-S100) adjuvant (NanoS100-SwIAV). As a control, a commercial SwIAV vaccine was included in a heterologous challenge infection trial. The frequencies of antigen-specific IL-17A and IFNγ secreting CD3+CD4lowCD8α+CD8ß+ memory T-helper cells were significantly increased in the lung draining tracheobronchial lymph nodes (TBLN) of intradermal, intramuscular and intranasal inoculated NanoS100-SwIAV vaccine and commercial vaccine administered animals. While the frequencies of antigen-specific, IFNγ secreting CD3+CD4lowCD8α+CD8ß+ memory T-helper cells were significantly enhanced in the blood of intranasal and intramuscular vaccinates. These observations suggest that the CD3+CD4lowCD8α+CD8ß+ T-helper/memory cells in pigs may have a protective and/or regulatory role/s in immune responses against SwIAV infection. These observations highlight the heterogeneity and plasticity of porcine CD4+ T-helper/memory cells in response to respiratory viral infection in pigs. Comprehensive systems immunology studies are needed to further decipher the cellular lineages and functional role/s of this porcine T helper/memory cell subset.

Recovery, separation and production of fuel, plastic and aluminum from the Tetra PAK waste to hydrothermal and pyrolysis processes.

The establishment of a method of separation of materials from Tetra Pak waste to obtain products for use as raw material, fuel or other purposes was investigated in this study. First, the feasibility of hydrothermal treatment for the production of a solid fuel (hydrochar) and solid fraction formed by polyethylene and aluminum, called composite was analyzed. The results indicated that hydrothermal treatment performed at 240 °C yield the formation of hydrochar with good properties for its use as fuel and a composite of polyethylene and aluminum. The best conversion and separation of the cardboard and polyethylene/aluminum were obtained using 120 min as operating time. Then, the recovery of the aluminum fraction from the composite by using spent olive oil waste was studied. A partial separation of the composite layers (polyethylene and aluminum) was accomplished with improved aluminum purity for higher operating temperatures. Finally, the operating conditions of the pyrolysis process for the production of a solid (char) and high purity composite (aluminum) were optimized. The characterization results indicated that both char and aluminum resulting from the pyrolysis of the Tetra Pak at 400 °C still have a significant amount of polyethylene while higher purity levels of aluminum can be obtained at temperatures equal of higher than 500 °C.