Celecoxib exhibits antifungal effect against Paracoccidioides brasiliensis both directly and indirectly by activating neutrophil responses.

BACKGROUND: Celecoxib, an anti-inflammatory drug, combined therapies using antimicrobials and immune modulator drugs are being studied. OBJECTIVE: To assess whether Celecoxib has direct in vitro antifungal effect against the Paracoccidioides brasiliensis, the causative agent of Paracoccidioidomycosis-(PCM) and also if it improves the in vivo activity of neutrophils-(PMN) in an experimental murine subcutaneous-(air pouch) model of the disease. METHODS: The antifungal activity of Celecoxib(6 mg/mL) on P. brasiliensis-(Pb18) was evaluated using the microdilution technique. Splenocytes co-cultured with Pb18 and treated with Celecoxib(6 mg/mL) were co-cultured for 24, 48 and 72-hours. Swiss mice were inoculated with Pb18 and treated with Celecoxib(6 mg/kg) in the subcutaneous air pouch. Neutrophils were collected from the air pouch. Mitochondrial activity, reactive oxygen production, catalase, peroxidase, cytokines and chemokines, nitrogen species, total protein, microbicidal activity of PMNs and viable Pb18 cells numbers were analyzed. RESULTS: Celecoxib had no cytotoxic effect on splenocytes co-cultured with Pb18, but had a marked direct antifungal effect, inhibiting fungal growth both in vitro and in vivo. Celecoxib interaction with immune system cells in the air pouch, it leads to activation of PMNs, as confirmed by several parameters (mitochondrial activity, reactive oxygen species, peroxidase, KC and IL-6 increase, killing constant and phagocytosis). Celecoxib was able to reduce IL-4, IL-10 and IL-12 cytokine production. The number of recovered viable Pb18 decreased dramatically. CONCLUSIONS: This is the first report of the direct antifungal activity of Celecoxib against P. brasiliensis. The use of Celecoxib opens a new possibility for future treatment of PCM.

Bovine serum albumin nanoparticles containing Poly (I:C) can enhance the neutralizing antibody response induced by envelope protein of Orthoflavivirus zikaense.

Since the Orthoflavivirus zikaense (ZIKV) has been considered a risk for Zika congenital syndrome development, developing a safe and effective vaccine has become a high priority. Numerous research groups have developed strategies to prevent ZIKV infection and have identified the domain III of the ZIKV envelope protein (zEDIII) as a promising target. Subunit antigens are often poorly immunogenic, necessitating the use of adjuvants and/or delivery systems to induce optimal immune responses. The subject of nanotechnology has substantial expansion in recent years in terms of research and applications. Nanoparticles could be used as drug delivery systems and to increase the immunogenicity and stability of a given antigen. This work aims to characterize and validate the potential of a vaccine formulation composed of domain zEDIII and bovine serum albumin nanoparticles containing polyinosinic-polycytidylic acid (NPPI). NPPI were uptake in vitro by immature bone marrow dendritic cells and histological analysis of the skin of mice treated with NPPI showed an increase in cellularity. Immunization assay showed that mice immunized with zEDIII in the presence of NPPI produced neutralizing antibodies. Through the passive transfer of sera from immunized mice to ZIKV-infected neonatal mice, it was demonstrated that these antibodies provide protection, mitigating weight loss, clinical or neurological signs induced by infection, and significantly increased survival rates. Protection was further substantiated by the reduction in the number of viable infectious ZIKV, as well as a decrease in inflammatory cytokines and tissue alterations in the brains of infected mice. Taken together, data presented in this study shows that NPPI + zEDIII is a promising vaccine candidate for ZIKV.

Serum albumin nanoparticles vaccine provides protection against a lethal Pseudomonas aeruginosa challenge.

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in immunocompromised individuals and in patients with cystic fibrosis. A range of vaccines to prevent infections caused by P. aeruginosa has already been tested, yet no vaccine against this pathogen is currently available. The goal of this study was to evaluate the potential of bovine serum albumin nanoparticles (BSA-NPs) associated with total P. aeruginosa ATCC 27853 antigens in inducing protection against the infection with virulent P. aeruginosa PA14 strain in murine model of nasal infection. Swiss mice were immunized with BSA-NPs associated with total P. aeruginosa antigens (NPPa) or empty NPs (NPe). As positive and negative control, groups of animals were immunized with total antigens of P. aeruginosa ATCC 27853 and phosphate buffered saline, respectively. Immunized mice were infected via nasal route using P. aeruginosa PA14 strain. The survival after 48 h was evaluated and the lungs from animals were processed for quantification of bacterial load, cytokine expression and histopathological analysis. After infection with P. aeruginosa PA14, animals immunized with NPPa had the highest survival rate, the lowest bacterial lung load, a controlled production of cytokines and few histopathological changes. These results indicate that NPPa immunization protected mice from infection, contributing for the elimination of the bacteria from the lungs, which consequently reflected the survival of the animals. Therefore, this vaccine was able to induce a functional response in an animal model of lethal infection and thereby is a promising platform for P. aeruginosa vaccines.