Browsing by Author "Covián, Camila"

Now showing 1 - 6 of 6
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    BCG-induced cross-protection and development of trained immunity: implication for vaccine design
    (2019) Covián, Camila; Fernández Fierro, Ayleen Lorena; Retamal Díaz, Angello Ricardo; Díaz Acevedo, Fabián Esteban; Vásquez Veloso, Abel; Lay Remolcoi, Margarita Kam-len; Riedel Soria, Claudia; González Muñoz, Pablo Alberto; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes
    The Bacillus Calmette-Guerin (BCG) is a live attenuated tuberculosis vaccine that has the ability to induce non-specific cross-protection against pathogens that might be unrelated to the target disease. Vaccination with BCG reduces mortality in newborns and induces an improved innate immune response against microorganisms other than Mycobacterium tuberculosis, such as Candida albicans and Staphylococcus aureus. Innate immune cells, including monocytes and natural killer (NK) cells, contribute to this non-specific immune protection in a way that is independent of memory T or B cells. This phenomenon associated with a memory-like response in innate immune cells is known as "trained immunity." Epigenetic reprogramming through histone modification in the regulatory elements of particular genes has been reported as one of the mechanisms associated with the induction of trained immunity in both, humans and mice. Indeed, it has been shown that BCG vaccination induces changes in the methylation pattern of histones associated with specific genes in circulating monocytes leading to a "trained" state. Importantly, these modifications can lead to the expression and/or repression of genes that are related to increased protection against secondary infections after vaccination, with improved pathogen recognition and faster inflammatory responses. In this review, we discuss BCG-induced cross-protection and acquisition of trained immunity and potential heterologous effects of recombinant BCG vaccines.
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    Contribution of resident memory CD8+ T cells to protective immunity against respiratory syncytial virus and their impact on vaccine design
    (2019) Retamal Díaz, Angello; Covián, Camila; Pacheco, Gaspar A.; Castiglione Matamala, Angelo T.; Bueno Ramírez, Susan; González, Pablo A.; Kalergis, Alexis M.
    Worldwide, human respiratory syncytial virus (RSV) is the most common etiological agent for acute lower respiratory tract infections (ALRI). RSV-ALRI is the major cause of hospital admissions in young children, and it can cause in-hospital deaths in children younger than six months old. Therefore, RSV remains one of the pathogens deemed most important for the generation of a vaccine. On the other hand, the effectiveness of a vaccine depends on the development of immunological memory against the pathogenic agent of interest. This memory is achieved by long-lived memory T cells, based on the establishment of an effective immune response to viral infections when subsequent exposures to the pathogen take place. Memory T cells can be classified into three subsets according to their expression of lymphoid homing receptors: central memory cells (T-CM), effector memory cells (T-EM) and resident memory T cells (T-RM). The latter subset consists of cells that are permanently found in non-lymphoid tissues and are capable of recognizing antigens and mounting an effective immune response at those sites. T-RM cells activate both innate and adaptive immune responses, thus establishing a robust and rapid response characterized by the production of large amounts of effector molecules. T-RM cells can also recognize antigenically unrelated pathogens and trigger an innate-like alarm with the recruitment of other immune cells. It is noteworthy that this rapid and effective immune response induced by T-RM cells make these cells an interesting aim in the design of vaccination strategies in order to establish T-RM cell populations to prevent respiratory infectious diseases. Here, we discuss the biogenesis of T-RM cells, their contribution to the resolution of respiratory viral infections and the induction of T-RM cells, which should be considered for the rational design of new vaccines against RSV.
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    Could BCG vaccination induce protective trained immunity for SARS-CoV-2?
    (2020) Covián, Camila; Retamal Díaz, Angello Ricardo; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes
    Trained immunity is a type of non-specific memory-like immune response induced by some pathogens and vaccines, such as BCG, which can confer antigen-independent protection against a wide variety of pathogens. The BCG vaccine has been extensively used to protect against tuberculosis for almost a 100 years. Interestingly, this vaccine reduces children's mortality caused by infections unrelated to Mycobacterium tuberculosis infection, a phenomenon thought to be due to the induction of trained immunity. The SARS-CoV-2 pandemic has infected, as of April 22, 2020, 2,623,231 people globally, causing a major public health problem worldwide. Currently, no vaccine or treatment is available to control this pandemic. We analyzed the number of positive cases and deaths in different countries and correlated them with the inclusion of BCG vaccination at birth in their national vaccination programs. Interestingly, those countries where BCG vaccination is given at birth have shown a lower contagion rate and fewer COVID-19-related deaths, suggesting that this vaccine may induce trained immunity that could confer some protection for SARS-CoV-2.
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    Induction of trained immunity by recombinant vaccines
    (Frontiers Media S.A., 2020) Covián, Camila; Rios Raggio, Mariana; Berríos Rojas, Roslye V.; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes
    Vaccines represent an important strategy to protect humans against a wide variety of pathogens and have even led to eradicating some diseases. Although every vaccine is developed to induce specific protection for a particular pathogen, some vaccine formulations can also promote trained immunity, which is a non-specific memory-like feature developed by the innate immune system. It is thought that trained immunity can protect against a wide variety of pathogens other than those contained in the vaccine formulation. The non-specific memory of the trained immunity-based vaccines (TIbV) seems beneficial for the immunized individual, as it may represent a powerful strategy that contributes to the control of pathogen outbreaks, reducing morbidity and mortality. A wide variety of respiratory viruses, including respiratory syncytial virus (hRSV) and metapneumovirus (hMPV), cause serious illness in children under 5 years old and the elderly. To address this public health problem, we have developed recombinant BCG vaccines that have shown to be safe and immunogenic against hRSV or hMPV. Besides the induction of specific adaptive immunity against the viral antigens, these vaccines could generate trained immunity against other respiratory pathogens. Here, we discuss some of the features of trained immunity induced by BCG and put forward the notion that recombinant BCGs expressing hRSV or hMPV antigens have the capacity to simultaneously induce specific adaptive immunity and non-specific trained immunity. These recombinant BCG vaccines could be considered as TIbV capable of inducing simultaneously the development of specific protection against hRSV or hMPV, as well as non-specific trained-immunity-based protection against other pathogenic viruses.
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    Interim report: Safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy chilean adults in a phase 3 clinical trial
    (2021) Bueno Ramírez, Susan; Abarca Villaseca, Katia; González Adonis, Pablo Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Soto Ramírez, Jorge Andrés; Duarte Peñaloza, Luisa Fernanda; Schultz Lombardic, Bárbara M.; Pacheco, Gaspar A.; González Carreño, Liliana Andrea; Vázquez, Yaneisi; Ríos Raggio, Mariana; Melo González, Felipe; Rivera Pérez, Daniela; Iturriaga, Carolina; Urzúa Acevedo, Marcela del Pilar; Domínguez De Landa, María Angélica; Andrade Parra, Catalina Andrea; Berríos Rojas, Roslye; Canedo Marroquín, Giselda; Covián, Camila
    The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.
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    Naturally derived heme-oxygenase 1 inducers and their therapeutic application to immune-mediated diseases
    (Frontiers Media S.A., 2020) Funes, Samanta Celeste; Rios Raggio, Mariana; Fernández Fierro, Ayleen Lorena; Covián, Camila; Bueno Ramírez, Susan; Riedel Soria, Claudia; Mackern Oberti, Juan Pablo; Kalergis Parra, Alexis Mikes
    Heme oxygenase (HO) is the primary antioxidant enzyme involved in heme group degradation. A variety of stimuli triggers the expression of the inducible HO-1 isoform, which is modulated by its substrate and cellular stressors. A major anti-inflammatory role has been assigned to the HO-1 activity. Therefore, in recent years HO-1 induction has been employed as an approach to treating several disorders displaying some immune alterations components, such as exacerbated inflammation or self-reactivity. Many natural compounds have shown to be effective inductors of HO-1 without cytotoxic effects; among them, most are chemicals present in plants used as food, flavoring, and medicine. Here we discuss some naturally derived compounds involved in HO-1 induction, their impact in the immune response modulation, and the beneficial effect in diverse autoimmune disorders. We conclude that the use of some compounds from natural sources able to induce HO-1 is an attractive lifestyle toward promoting human health. This review opens a new outlook on the investigation of naturally derived HO-1 inducers, mainly concerning autoimmunity.