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1.
Clin Vaccine Immunol ; 22(9): 1004-12, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26135973

RESUMEN

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8(+) T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines.


Asunto(s)
Inmunidad Adaptativa , Adyuvantes Inmunológicos , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Resinas Acrílicas , Adyuvantes Inmunológicos/administración & dosificación , Animales , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Linfocitos T CD8-positivos/inmunología , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/inmunología , Vacunas contra la Influenza/administración & dosificación , Lecitinas/inmunología , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Moléculas de Patrón Molecular Asociado a Patógenos , Balance Th1 - Th2 , Vacunación
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