Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
Phytomedicine ; 64: 152927, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31465981


BACKGROUND: Next to aluminum salts, squalene nanoemulsions comprise the most widely employed class of adjuvants in approved vaccines. Despite their importance, the mechanisms of action of squalene nanoemulsions are not completely understood, nor are the structure/function requirements of the oil composition. PURPOSE: In this study, we build on previous work that compared the adjuvant properties of nanoemulsions made with different classes of oil structures to squalene nanoemulsion. Here, we introduce nanoemulsions made with polyprenols derived from species of the Pinaceae family as novel vaccine adjuvant compositions. In contrast with long-chain triglycerides that do not efficiently enhance an immune response, both polyprenols and squalene are comprised of multimeric isoprene units, which may represent an important structural property of oils in nanoemulsions with adjuvant properties. STUDY DESIGN: Oils derived from species of the Pinaceae family were formulated in nanoemulsions, with or without a synthetic Toll-like receptor 4 (TLR4) ligand, and characterized regarding physicochemical and biological activity properties in comparison to squalene nanoemulsions. METHODS: Oils were extracted from species of the Pinaceae family and used to prepare oil-in-water nanoemulsions by microfluidization. Emulsion droplet diameter stability was characterized by dynamic light scattering. Nanoemulsions were evaluated for in vitro biological activity using human whole blood, and in vivo biological activity in mouse, pig, and ferret models when combined with pandemic influenza vaccine antigens. RESULTS: Nanoemulsions comprised of Pinaceae-derived polyprenol oils demonstrated long-term physical stability, stimulated cytokine production from human cells in vitro, and promoted antigen-specific immune responses in various animal models, particularly when formulated with the TLR4 ligand glucopyranosyl lipid adjuvant (GLA). CONCLUSION: Pinaceae-derived nanoemulsions are compatible with inclusion of a synthetic TLR4 ligand and promote antigen-specific immune responses to pandemic influenza antigens in mouse, pig, and ferret models.

Adyuvantes Inmunológicos/farmacología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Pinaceae/química , Aceites de Plantas/farmacología , Poliprenoles/farmacología , Escualeno/farmacología , Adyuvantes Inmunológicos/química , Animales , Emulsiones , Femenino , Hurones , Humanos , Gripe Humana/virología , Masculino , Ratones , Ratones Endogámicos C57BL , Aceites de Plantas/química , Poliprenoles/química , Organismos Libres de Patógenos Específicos , Escualeno/química , Porcinos , Receptor Toll-Like 4/inmunología
J Control Release ; 244(Pt A): 98-107, 2016 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-27847326


For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.

Adyuvantes Inmunológicos/química , Hidróxido de Aluminio/química , Óxido de Aluminio/química , Imidazoles/química , Nanopartículas/química , Quinolinas/química , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 8/metabolismo , Vacunas contra el SIDA/inmunología , Adsorción , Animales , Estabilidad de Medicamentos , Humanos , Imidazoles/inmunología , Inmunidad Celular , Inmunidad Humoral , Ligandos , Lípidos/química , Ratones , Ratones Endogámicos C57BL , Tamaño de la Partícula , Quinolinas/inmunología , Propiedades de Superficie , Vacunas contra la Tuberculosis/inmunología
Hum Vaccin Immunother ; 12(4): 1009-26, 2016 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-26618392


Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

Adyuvantes Inmunológicos , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza , Transferencia de Tecnología , Evaluación Preclínica de Medicamentos , Emulsiones/química , Humanos , Subtipo H5N1 del Virus de la Influenza A/fisiología , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Aceites , Pandemias/prevención & control , Rumanía , Virión/fisiología , Inactivación de Virus