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.

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia, yet the immune mechanisms required for protection against invasive pulmonary infection remain incompletely understood. Using a murine model of homologous protection against invasive pneumococcal pneumonia, we investigated the relative contribution of humoral and cellular immunity through adoptive serum transfer, immune cell depletion, and lung transcriptional profiling. Passive transfer of immune serum conferred robust protection, whereas neutrophil depletion impaired bacterial control, demonstrating that antibodies and neutrophils are key mediators of protection. In contrast, depletion of CD4+ T cells or NK cells did not compromise survival. Although IL-17A has been widely implicated in host defense against pneumococcal infection, IL-17A- deficient mice remained protected, albeit with delayed clearance and reduced early antibody responses. This delay was associated with compensatory upregulation of IL-17F and increased expression of Th1-associated genes in the lung. Together, these findings indicate that IL-17A is not essential for protection and support a model in which coordinated Th1 and Th17-related cytokine responses collectively promote neutrophil recruitment and effective antibody-mediated defense. These results highlight functional redundancy within the IL-17 cytokine axis and suggest that integrated cytokine networks, rather than individual mediators, underpin protective immunity to pneumococcal pneumonia, with implications for next-generation vaccine design.

Streptococcus pneumoniae is a leading cause of community-acquired pneumonia, yet the immune mechanisms required for protection against invasive pulmonary infection remain inadequately understood. Using a murine model of homologous protection against invasive pneumococcal pneumonia, we explored the relative contributions of humoral and cellular immunity using adoptive serum transfer, immune cell depletion, and lung transcriptional profiling. Our findings indicated that passive transfer of immune serum provided robust protection, while neutrophil depletion significantly compromised bacterial control, highlighting that both antibodies and neutrophils are key mediators of protection. In contrast, depletion of CD4⁺ T cells or NK cells did not compromise survival. Although IL-17A has been widely implicated in host defense against pneumococcal infection, IL-17A-deficient mice remained protected, albeit with delayed clearance and reduced early antibody responses. We associate this delay with compensatory upregulation of IL-17F and increased expression of Th1-associated genes in the lungs. Together, these findings indicate that IL-17A is not essential for protection and support a model in which coordinated Th1- and Th17-related cytokine responses collectively promote neutrophil recruitment and effective antibody-mediated defense. These results highlight functional redundancy within the IL-17 cytokine axis and suggest that integrated cytokine networks, rather than individual mediators, underpin protective immunity to pneumococcal pneumonia, with implications for next-generation vaccine design.