https://hdl.handle.net/20.500.12008/41704 2026-05-13T15:16:06Z https://hdl.handle.net/20.500.12008/54969 Título: Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice Autor: Bascuas, Thais; Moreno, María; Grille, Sofía; Chabalgoity, José A. Resumen: We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients’ conditions. In this work, we assessed the effi cacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP–Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immuno therapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting. 2018-01-01T00:00:00Z https://hdl.handle.net/20.500.12008/54960 Título: Intranasal Delivery of Quillaja brasiliensis Saponin-Based Nanoadjuvants Improve Humoral Immune Response of Influenza Vaccine in Aged Mice Autor: Silveira, Fernando; García, Florencia; García, Gabriel; Chabalgoity, José A.; Rossi, Silvina; Baz, Mariana Resumen: Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines. 2024-01-01T00:00:00Z https://hdl.handle.net/20.500.12008/54959 Título: Bacterial Lysates as Immunotherapies for Respiratory Infections: Methods of Preparation Autor: Suárez, Norma; Ferrara, Florencia; Rial, Analia; Dee, Valerie; Chabalgoity, Jose A. Resumen: Bacterial lysates, prepared from the microorganisms most frequently involved in human Respiratory Tract Infections (RTIs) have been in the market for several decades, and at present, several different brands are available in many countries worldwide. They all claimed to exert local and systemic immunomodulatory effects but different clinical trials show disparate results between them. The lack of consistency of predicted therapeutic effects has undermined their clinical use and hampered licensing in several countries.One explanation for such lack of consistency in the results is that their methods of preparation are also very different. Here, we review the available literature describing methods of preparation of bacterial lysates, including patent disclosure documents. We found a great variety of methodologies of preparation and a lack of standardized procedures among them. The main conclusion of our study is that there is a clear need for standardized protocols of production to obtain comparable results in clinical trials worldwide. 2020-01-01T00:00:00Z https://hdl.handle.net/20.500.12008/54958 Título: Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation Autor: Ferrara, Florencia; Rial, Analía; Suárez, Norma; Chabalgoity, José Alejandro Resumen: Polyvalent bacterial lysates have been in use for decades for prevention and treatment of respiratory infections with reported clinical benefits. However, besides claims of broad immune activation, the mode of action is still a matter of debate. The lysates, formulated with the main bacterial species involved in respiratory infections, are commonly prepared by chemical or mechanical disruption of bacterial cells, what is believed influences the biological activity of the product. Here, we prepared two polyvalent lysates with the same composition but different method of bacterial cell disruption and evaluated their biological activity in a comparative fashion. We found that both bacterial lysates induce NF-kB activation in a MyD88 dependent manner, suggesting they work as TLR agonists. Further, we found that a single intranasal dose of any of the two lysates, is sufficient to protect against pneumococcal pneumonia, suggesting that they exert similar biological activity. We have previously shown that protection against pneumococcal pneumonia can also be induced by prior S. pneumoniae sub lethal infection or therapeutic treatment with a TLR5 agonist. Protection in those cases depends on neutrophil recruitment to the lungs, and can be associated with increased local expression of IL-17A. Here, we show that bacterial lysates exert protection against pneumococcal pneumonia independently of neutrophils, IL-17A or Caspase-1/11 activation, suggesting the existence of redundant mechanisms of protection. Trypsin-treated lysates afford protection to the same extent, suggesting that just small peptides suffice to exert the protective effect or that the molecules responsible for the protective effect are not proteins. Understanding the mechanism of action of bacterial lysates and deciphering the active components shall allow redesigning them with more precisely defined formulations and expanding their range of action. 2021-01-01T00:00:00Z