ISCOM-like Nanoparticles Formulated with Quillaja brasiliensis Saponins Are Promising Adjuvants for Seasonal Influenza Vaccines

Abstract

Vaccination is the most effective public health intervention to prevent influenza infections, which are responsible for an important burden of respiratory illnesses and deaths each year. Currently, licensed influenza vaccines are mostly split inactivated, although in order to achieve higher efficacy rates, some influenza vaccines contain adjuvants. Although split-inactivated vaccines induce mostly humoral responses, tailoring mucosal and cellular immune responses is crucial for preventing influenza infections. Quillaja brasiliensis saponin-based adjuvants, including ISCOM-like nanoparticles formulated with the QB-90 saponin fraction (IQB90), have been studied in preclinical models for more than a decade and have been demonstrated to induce strong humoral and cellular immune responses towards several viral antigens. Herein, we demonstrate that a split-inactivated IQB90 adjuvanted influenza vaccine triggered a protective immune response, stronger than that induced by a commercial unadjuvanted vaccine, when applied either by the subcutaneous or the intranasal route. Moreover, we reveal that this novel adjuvant confers up to a ten-fold dose-sparing effect, which could be crucial for pandemic preparedness. Last but not least, we assessed the role of caspase-1/11 in the generation of the immune response triggered by the IQB90 adjuvanted influenza vaccine in a mouse model and found that the cellular-mediated immune response triggered by the IQB90-Flu relies, at least in part, on a mechanism involving the casp-1/11 pathway but not the humoral response elicited by this formulation.

Peptide Vaccines in Melanoma: Chemical Approaches towards Improved Immunotherapeutic Efficacy

“…40 nm size, and obtained a combination of antigens, cholesterol, phospholipid and the Quillaja saponaria saponin. This combination results in a hydrophobic interaction between the lipids and the antigen [ 138 ].…”

Development of Nasal Vaccines and the Associated Challenges

“…ISCOMs-based vaccines containing influenza virus, Mycobacterium tuberculosis , RSV, and measles antigen have been indicated to effectively induce an immune response in the body after nasal/pulmonary vaccination, producing high titers of IgA in the nasal cavity and the lung [ 197 , 198 , 199 , 200 , 201 , 202 , 203 ]. In certain cases, this local mucosal inoculation produces greater immunity compared to that produced upon injectable vaccination.…”

Quillaja brasiliensis nanoparticle adjuvant formulation improves the efficacy of an inactivated trivalent influenza vaccine in mice

“…Over the last decade, our research team has been studying saponins extracted from the leaves of Quillaja brasiliensis (QB) as an alternative to saponins extracted from Quillaja saponaria tree bark ( 9 , 20 – 23 ). Comprehensive chemical characterization has shown that the two species share a myriad of saponin structures, including well-known saponins with high immunoadjuvant activity, as well as QS-21 ( 12 , 21 , 24 ), a potent adjuvant isolated from the Q. saponaria tree and which is currently used in a few licensed vaccines ( 8 , 10 , 25 ).…”

“…Comprehensive chemical characterization has shown that the two species share a myriad of saponin structures, including well-known saponins with high immunoadjuvant activity, as well as QS-21 ( 12 , 21 , 24 ), a potent adjuvant isolated from the Q. saponaria tree and which is currently used in a few licensed vaccines ( 8 , 10 , 25 ). Furthermore, several studies have shown the immunoadjuvant potential of saponins from QB and their ability to form ISCOM-like nanostructures ( 9 , 11 , 21 , 22 , 26 ). Thus, leaves of QB are a readily renewable source of these important secondary metabolites of high added value and of relevant importance for public health ( 9 , 26 ).…”

“…Furthermore, several studies have shown the immunoadjuvant potential of saponins from QB and their ability to form ISCOM-like nanostructures ( 9 , 11 , 21 , 22 , 26 ). Thus, leaves of QB are a readily renewable source of these important secondary metabolites of high added value and of relevant importance for public health ( 9 , 26 ).…”