Arenavirus-Based Vectors Generate Robust SIV Immunity in Non-Human Primates.

Arenavirus-based vectors are being investigated as therapeutic vaccine candidates with the potential to elicit robust CD8 T-cell responses. We compared the immunogenicity of replicating (artPICV and artLCMV) and non-replicating (rPICV and rLCMV) arenavirus-based vectors expressing simian immunodeficiency virus (SIV) Gag and Envelope (Env) immunogens in treatment-naïve non-human primates. Heterologous regimens with non-replicating and replicating vectors elicited more robust SIV IFN-γ responses than a homologous regimen, and replicating vectors elicited significantly higher cellular immunogenicity than non-replicating vectors. The heterologous regimen elicited high anti-Env antibody titers when administered intravenously, with replicating vectors inducing significantly higher titers than non-replicating vectors. Intramuscular immunization resulted in more durable antibody responses than intravenous immunization for both vector platforms, with no difference between the replicating and non-replicating vectors. Overall, both replicating and non-replicating arenavirus vectors generated robust T- and B-cell-mediated immunity to SIV antigens in treatment-naïve non-human primates, supporting further evaluation of these vectors in a clinical setting for HIV therapy.

Immunogenic arenavirus vector SIV vaccine reduces setpoint viral load in SIV-challenged rhesus monkeys.

HIV affects more than 38 million people worldwide. Although HIV can be effectively treated by lifelong combination antiretroviral therapy, only a handful of patients have been cured. Therapeutic vaccines that induce robust de novo immune responses targeting HIV proteins and latent reservoirs will likely be integral for functional HIV cure. Our study shows that immunization of naïve rhesus macaques with arenavirus-derived vaccine vectors encoding simian immunodeficiency virus (SIVSME543 Gag, Env, and Pol) immunogens is safe, immunogenic, and efficacious. Immunization induced robust SIV-specific CD8+ and CD4+ T-cell responses with expanded cellular breadth, polyfunctionality, and Env-binding antibodies with antibody-dependent cellular cytotoxicity. Vaccinated animals had significant reductions in median SIV viral load (1.45-log10 copies/mL) after SIVMAC251 challenge compared with placebo. Peak viral control correlated with the breadth of Gag-specific T cells and tier 1 neutralizing antibodies. These results support clinical investigation of arenavirus-based vectors as a central component of therapeutic vaccination for HIV cure.

Distinct Proteomic Signatures in 16 HDL (High-Density Lipoprotein) Subspecies.

Objective- HDL (high-density lipoprotein) in plasma is a heterogeneous group of lipoproteins typically containing apo AI as the principal protein. Most HDLs contain additional proteins from a palate of nearly 100 HDL-associated polypeptides. We hypothesized that some of these proteins define distinct and stable apo AI HDL subspecies with unique proteomes that drive function and associations with disease. Approach and Results- We produced 17 plasma pools from 80 normolipidemic human participants (32 men, 48 women; aged 21-66 years). Using immunoaffinity isolation techniques, we isolated apo AI containing species from plasma and then used antibodies to 16 additional HDL protein components to isolate compositional subspecies. We characterized previously described HDL subspecies containing apo AII, apo CIII, and apo E; and 13 novel HDL subspecies defined by presence of apo AIV, apo CI, apo CII, apo J, α-1-antitrypsin, α-2-macroglobulin, plasminogen, fibrinogen, ceruloplasmin, haptoglobin, paraoxonase-1, apo LI, or complement C3. The novel species ranged in abundance from 1% to 18% of total plasma apo AI. Their concentrations were stable over time as demonstrated by intraclass correlations in repeated sampling from the same participants over 3 to 24 months (0.33-0.86; mean 0.62). Some proteomes of the subspecies relative to total HDL were strongly correlated, often among subspecies defined by similar functions: lipid metabolism, hemostasis, antioxidant, or anti-inflammatory. Permutation analysis showed that the proteomes of 12 of the 16 subspecies differed significantly from that of total HDL. Conclusions- Taken together, correlation and permutation analyses support speciation of HDL. Functional studies of these novel subspecies and determination of their relation to diseases may provide new avenues to understand the HDL system of lipoproteins.

Caracterización farmacognóstica de Indigofera suffruticosa Mill (añil cimarrón) / Pharmacognostic characterization of Indigofera suffructicosa Mill. (wild indigo)

Las investigaciones para obtener principios activos son largas y costosas y una preparación de planta bien estandarizada puede ser muy efectiva, por lo que en la actualidad, la utilización de extractos totales ha demostrado en muchos casos un efecto más beneficioso en el organismo humano que la acción del compuesto aislado. Se efectuaron las investigaciones para obtener la droga vegetal de Indigofera suffruticosa Mill. (añil cimarrón) debidamente caracterizada, con vistas a obtenerla con la calidad requerida. Para ello se realizaron descripciones macro y micromorfológica de la especie, el estudio de secado, se determinaron los índices numéricos, según normas internacionales para drogas vegetales. En los resultados, se estableció la presencia mayoritaria de flavonoides, coumarinas y triterpenos, se estandarizó un perfil cromatográfico para compuestos flavonoides. Además, se comprobó que el período óptimo de conservación de la droga vegetal es un tiempo de 10 meses en frascos de polipropileno(AU)

Caracterización farmacognóstica de Indigofera suffruticosa Mill (añil cimarrón). / Pharmacognostic characterization of Indigofera suffructicosa Mill (wild indigo).

Las investigaciones para obtener principios activos son largas y costosas y una preparación de planta bien estandarizada puede ser muy efectiva, por lo que en la actualidad, la utilización de extractos totales ha demostrado en muchos casos un efecto más beneficioso en el organismo humano que la acción del compuesto aislado. Se efectuaron las investigaciones para obtener la droga vegetal de Indigofera suffruticosa Mill. (añil cimarrón) debidamente caracterizada, con vistas a obtenerla con la calidad requerida. Para ello se realizaron descripciones macro y micromorfológica de la especie, el estudio de secado, se determinaron los índices numéricos, según normas internacionales para drogas vegetales. En los resultados, se estableció la presencia mayoritaria de flavonoides, coumarinas y triterpenos, se estandarizó un perfil cromatográfico para compuestos flavonoides. Además, se comprobó que el período óptimo de conservación de la droga vegetal es un tiempo de 10 meses en frascos de polipropileno.

The researches to achieve active principles are long and expensive, and a well standardized plant preparation could be very efficacious. That is why nowadays the use of total extracts has showed, in many instances, a more beneficial effect in human organism than the action of an isolated compound. Researches have been conducted to obtain a properly plant drug from Indigofera suffruticosa Mill (wild indigo) with the required quality. To this end, macro- and micromorphologic descriptions of species were made, a drying study was undertaken, and the numerical indexes were determined, according to the international standards for plant drugs. In the results, it was observed a predominance of flavonoids, coumarins, and tryterpenes, and a chromatographic profile was standardized for flavonoid compounds. It was also confirmed that the optimal period of preservation of the plant drug is 10 months in polypropylene flasks.