Examinando por Autor "Montero, David A."
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Ítem A chimeric protein-based vaccine elicits a strong IgG antibody response and confers partial protection against Shiga toxin-producing Escherichia coli in mice(Frontiers Media SA, 2023) Montero, David A.; Garcia-Betancourt, Richard; Vidal, Roberto M.; Velasco, Juliana; Palacios, Pablo A.; Schneider, Daniela; Vega, Carolina; Gómez, Leonardo; Montecinos, Hernán; Soto-Shara, Rodrigo; Oñate, Ángel; Carreño, Leandro J.Background: Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen that causes gastrointestinal infections, ranging from acute diarrhea and dysentery to life-threatening diseases such as Hemolytic Uremic Syndrome. Currently, a vaccine to prevent STEC infection is an unmet medical need. Results: We developed a chimeric protein-based vaccine targeting seven virulence factors of STEC, including the Stx2B subunit, Tir, Intimin, EspA, Cah, OmpT, and AggA proteins. Immunization of mice with this vaccine candidate elicited significant humoral and cellular immune responses against STEC. High levels of specific IgG antibodies were found in the serum and feces of immunized mice. However, specific IgA antibodies were not detected in either serum or feces. Furthermore, a significantly higher percentage of antigen-specific CD4+ T cells producing IFN-γ, IL-4, and IL-17 was observed in the spleens of immunized mice. Notably, the immunized mice showed decreased shedding of STEC O157:H7 and STEC O91:H21 strains and were protected against weight loss during experimental infection. Additionally, infection with the STEC O91:H21 strain resulted in kidney damage in control unimmunized mice; however, the extent of damage was slightly lower in immunized mice. Our findings suggest that IgG antibodies induced by this vaccine candidate may have a role in inhibiting bacterial adhesion and complement-mediated killing. Conclusion: This study provides evidence that IgG responses are involved in the host defense against STEC. However, our results do not rule out that other classes of antibodies also participate in the protection against this pathogen. Additional work is needed to improve the protection conferred by our vaccine candidate and to elucidate the relevant immune responses that lead to complete protection against this pathogen. Copyright © 2023 Montero, Garcia-Betancourt, Vidal, Velasco, Palacios, Schneider, Vega, Gómez, Montecinos, Soto-Shara, Oñate and Carreño.Ítem Locus of Adhesion and Autoaggregation (LAA), a pathogenicity island present in emerging Shiga Toxin-producing Escherichia coli strains(Nature Publishing Group, 2017-12) Montero, David A.; Velasco, Juliana; Del Canto, Felipe; Puente, Jose L.; Padola, Nora L.; Rasko, David A.; Farfán, Mauricio; Salazar, Juan C.; Vidal, RobertoShiga Toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens associated with diarrhea, dysentery, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). Shiga toxins are the major virulence factor of these pathogens, however adhesion and colonization to the human intestine is required for STEC pathogenesis. A subset of STEC strains carry the Locus of Enterocyte Effacement (LEE) pathogenicity island (PAI), which encodes genes that mediate the colonization of the human intestine. While LEE-positive STEC strains have traditionally been associated with human disease, the burden of disease caused by STEC strains that lacks LEE (LEE-negative) has increased recently in several countries; however, in the absence of LEE, the molecular pathogenic mechanisms by STEC strains are unknown. Here we report a 86-kb mosaic PAI composed of four modules that encode 80 genes, including novel and known virulence factors associated with adherence and autoaggregation. Therefore, we named this PAI as Locus of Adhesion and Autoaggregation (LAA). Phylogenomic analysis using whole-genome sequences of STEC strains available in the NCBI database indicates that LAA PAI is exclusively present in a subset of emerging LEE-negative STEC strains, including strains isolated from HC and HUS cases. We suggest that the acquisition of this PAI is a recent evolutionary event, which may contribute to the emergence of these STEC. © 2017 The Author(s).Ítem Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies(Frontiers Media SA, 2024) Gutiérrez-Vera, Cristián; García-Betancourt, Richard; Palacios, Pablo A.; Müller, Marioly; Montero, David A.; Verdugo, Carlos; Ortiz, Francisca; Simon, Felipe; Kalergis, Alexis M.; González, Pablo A.; Saavedra-Avila, Noemi A.; Porcelli, Steven A.; Carreño, Leandro J.Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells.Ítem Two centuries of vaccination: historical and conceptual approach and future perspectives(Frontiers Media SA, 2023) Montero, David A.; Vidal, Roberto M.; Velasco, Juliana; Carreño, Leandro J.; Torres, Juan P.; Benachi O, Manuel A.; Tovar-Rosero, Yenifer-Yadira; Oñate, Angel A.; O'Ryan, MiguelOver the past two centuries, vaccines have been critical for the prevention of infectious diseases and are considered milestones in the medical and public health history. The World Health Organization estimates that vaccination currently prevents approximately 3.5–5 million deaths annually, attributed to diseases such as diphtheria, tetanus, pertussis, influenza, and measles. Vaccination has been instrumental in eradicating important pathogens, including the smallpox virus and wild poliovirus types 2 and 3. This narrative review offers a detailed journey through the history and advancements in vaccinology, tailored for healthcare workers. It traces pivotal milestones, beginning with the variolation practices in the early 17th century, the development of the first smallpox vaccine, and the continuous evolution and innovation in vaccine development up to the present day. We also briefly review immunological principles underlying vaccination, as well as the main vaccine types, with a special mention of the recently introduced mRNA vaccine technology. Additionally, we discuss the broad benefits of vaccines, including their role in reducing morbidity and mortality, and in fostering socioeconomic development in communities. Finally, we address the issue of vaccine hesitancy and discuss effective strategies to promote vaccine acceptance. Research, collaboration, and the widespread acceptance and use of vaccines are imperative for the continued success of vaccination programs in controlling and ultimately eradicating infectious diseases. Copyright © 2024 Montero, Vidal, Velasco, Carreño, Torres, Benachi O., Tovar-Rosero, Oñate and O'RyanÍtem Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development(Frontiers Media SA, 2023) Montero, David A.; Vidal, Roberto M.; Velasco, Juliana; George, Sergio; Lucero, Yalda; Gómez, Leonardo A.; Carreño, Leandro J.; García-Betancourt, Richard; O’Ryan, MiguelVibrio cholerae is the causative agent of cholera, a highly contagious diarrheal disease affecting millions worldwide each year. Cholera is a major public health problem, primarily in countries with poor sanitary conditions and regions affected by natural disasters, where access to safe drinking water is limited. In this narrative review, we aim to summarize the current understanding of the evolution of virulence and pathogenesis of V. cholerae as well as provide an overview of the immune response against this pathogen. We highlight that V. cholerae has a remarkable ability to adapt and evolve, which is a global concern because it increases the risk of cholera outbreaks and the spread of the disease to new regions, making its control even more challenging. Furthermore, we show that this pathogen expresses several virulence factors enabling it to efficiently colonize the human intestine and cause cholera. A cumulative body of work also shows that V. cholerae infection triggers an inflammatory response that influences the development of immune memory against cholera. Lastly, we reviewed the status of licensed cholera vaccines, those undergoing clinical evaluation, and recent progress in developing next-generation vaccines. This review offers a comprehensive view of V. cholerae and identifies knowledge gaps that must be addressed to develop more effective cholera vaccines. Copyright © 2023 Montero, Vidal, Velasco, George, Lucero, Gómez, Carreño, García-Betancourt and O’Ryan.