Browsing by Author "Gálvez Arriagada, Nicolás Marcelo Salvador"
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- ItemAntibody development for preventing the human respiratory syncytial virus pathology.(2020) Soto Ramírez, Jorge Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Pacheco, Gaspar A.; Bueno Ramírez, Susan; Kalergis Parra, Alexis MikesAbstract Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.Abstract Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.Abstract Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.Abstract Human respiratory syncytial virus (hRSV) is the most important etiological agent causing hospitalizations associated with respiratory diseases in children under 5 years of age as well as the elderly, newborns and premature children are the most affected populations. This viral infection can be associated with various symptoms, such as fever, coughing, wheezing, and even pneumonia and bronchiolitis. Due to its severe symptoms, the need for mechanical ventilation is not uncommon in clinical practice. Additionally, alterations in the central nervous system -such as seizures, encephalopathy and encephalitis- have been associated with cases of hRSV-infections. Furthermore, the absence of effective vaccines or therapies against hRSV leads to elevated expenditures by the public health system and increased mortality rates for the high-risk population. Along these lines, vaccines and therapies can elicit different responses to this virus. While hRSV vaccine candidates seek to promote an active immune response associated with the achievement of immunological memory, other therapies -such as the administration of antibodies- provide a protective environment, although they do not trigger the activation of the immune system and therefore do not promote an immunological memory. An interesting approach to vaccination is the use of virus-neutralizing antibodies, which inhibit the entry of the pathogen into the host cells, therefore impairing the capacity of the virus to replicate. Currently, the most common molecule targeted for antibody design against hRSV is the F protein of this virus. However, other molecular components of the virus -such as the G or the N hRSV proteins- have also been explored as potential targets for the control of this disease. Currently, palivizumab is the only monoclonal antibody approved for human use. However, studies in humans have shown a protective effect only after the administration of at least 3 to 5 doses, due to the stability of this vaccine. Furthermore, other studies suggest that palivizumab only has an effectiveness close to 50% in high-risk infants. In this work, we will review different strategies addressed for the use of antibodies in a prophylactic or therapeutic context and their ability to prevent the symptoms caused by hRSV infection of the airways, as well as in other tissues such as the CNS.
- ItemContribution of hypoxia inducible factor-1 during viral infections(2020) Reyes Muñoz, Antonia Paz; Corrales Bonilla, Nicolás; Gálvez Arriagada, Nicolás Marcelo Salvador; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes; González Muñoz, Pablo AlbertoHypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays critical roles during the cellular response to hypoxia. Under normoxic conditions, its function is tightly regulated by the degradation of its alpha subunit (HIF-1α), which impairs the formation of an active heterodimer in the nucleus that otherwise regulates the expression of numerous genes. Importantly, HIF-1 participates in both cancer and infectious diseases unveiling new therapeutic targets for those ailments. Here, we discuss aspects related to the activation of HIF-1, the effects of this transcription factor over immune system components, as well as the involvement of HIF-1 activity in response to viral infections in humans. Although HIF-1 is currently being assessed in numerous clinical settings as a potential therapy for different diseases, up to date, there are no clinical studies evaluating the pharmacological modulation of this transcription factor as a possible new antiviral treatment. However, based on the available evidence, clinical trials targeting this molecule are likely to occur soon. In this review we discuss the role of HIF-1 in viral immunity, the modulation of HIF-1 by different types of viruses, as well as the effects of HIF-1 over their life cycle and the potential use of HIF-1 as a new target for the treatment of viral infections.
- ItemDevelopment of recombinant vaccines to prevent the disease caused by the respiratory viruses SARS-CoV-2, hMPV, and hRSV(2022) Gálvez Arriagada, Nicolás Marcelo Salvador; Kalergis Parra, Alexis Mikes; Pontificia Universidad Católica de Chile. Facultad de Ciencias BiológicasLas infecciones respiratorias se encuentran entre las enfermedades más comunes en todo el mundo y el SARS-CoV-2, hRSV y hMPV son los principales virus que aumentan estas cifras. El SARS-CoV-2 es el agente viral responsable del COVID-19 y de la actual pandemia en curso en todo el mundo. Se han generado varias vacunas para enfrentar esta pandemia, pero se ha demostrado que la aparición de variantes de interés reduce la inmunidad inducida por la vacuna contra el SARS-CoV-2. El hMPV y el hRSV son las principales causas de infecciones agudas del tracto respiratorio inferior, con tasas significativas de morbilidad y mortalidad en poblaciones pediátricas y geriátricas, pero a pesar de su impacto en todo el mundo, hasta la fecha no se han aprobado vacunas contra estos dos virus. Mycobacterium bovis bacillus Calmette-Guérin (BCG) es la vacuna actualmente utilizada contra la Tuberculosis. Esta vacuna suele administrarse a recién nacidos y tiene perfiles de seguridad e inmunogenicidad ampliamente descritos. BCG promueve una polarización Th1 de células T CD4+, y se ha utilizado como vector para la expresión de antígenos heterólogos, con correlatos positivos de protección contra diferentes patógenos intracelulares. Esto condujo al uso de diferentes BCG recombinantes (rBCG) como vectores para la expresión de antígenos virales, con el fin de inducir respuestas inmunes polarizadas Th1 contra los virus correspondientes. Aquí se reporta el desarrollo y la caracterización de tres prototipos de vacunas rBCG diferentes. En primer lugar, se generó una cepa de rBCG que expresa la Nucleoproteína del SARS-CoV-2 (rBCG-N-SARS-CoV-2) y se evaluó su seguridad e inmunogenicidad. Se probaron esquemas de vacunación heterólogos para potenciar la respuesta inmunitaria provocada tras la vacunación. Esta vacuna demostró ser segura, detectándose importantes respuestas inmunitarias celulares y humorales, caracterizadas por la activación de células T CD4+ y CD8+, aumento de la secreción de citoquinas relacionadas con una respuesta Th1 y aumento de la secreción de anticuerpos anti-N-SARS-CoV-2. Estos datos sugieren que este prototipo de vacuna podría ser una plataforma eficaz para prevenir la enfermedad causada por el SARS-CoV-2 y ayudar a reducir el impacto de esta pandemia a nivel mundial. Se evaluaron la eficacia y la inmunogenicidad de una rBCG que expresa la fosfoproteína de hMPV (rBCG-P-hMPV) en un proceso buenas prácticas de manufactura (cGMP). La vacuna cGMP rBCG-P-hMPV fue segura e indujo una respuesta inmune humoral y celular protectora en ratones, como lo demuestra un menor número de cargas virales e infiltración de células en los pulmones, un aumento significativo en la activación de las células T, la secreción de citocinas proinflamatorias en su mayoría relacionadas con un perfil Th1, y la secreción de anticuerpos IgG e IgA contra hMPV. Estos resultados serán una piedra angular para la proyección de esta vacuna en ensayos clínicos con humanos. Reportes anteriores muestran que la inmunización con una cGMP rBCG que expresa la nucleoproteína del hRSV (rBCG-N-hRSV) protege contra este virus en ratones. En Chile se realizó un ensayo clínico fase 1 para evaluar la seguridad e inmunogenicidad de esta vacuna. Las muestras obtenidas se utilizaron para caracterizar la respuesta inmunitaria provocada tras la vacunación. Se detectó una respuesta celular significativamente mayor en diferentes momentos, junto con mayores niveles de anticuerpos circulantes contra antígenos de Mycobacterium y hRSV. Estos resultados caracterizan aún más la respuesta inmune provocada en humanos por esta vacuna contra hRSV. El desarrollo y caracterización de todas estas vacunas serán datos valiosos para la generación de tratamientos profilácticos seguros y efectivos contra estos virus respiratorios, que posiblemente podrían ser administrados a la población pediátrica.
- ItemHost components that modulate the disease caused by hmpv(MDPI AG, 2021) Gálvez Arriagada, Nicolás Marcelo Salvador; Andrade Parra, Catalina Andrea; Pacheco Ruidiaz, Gaspar Andrés; Soto Ramírez, Jorge Andrés; Stranger Mac-kinnon, Vicente; Rivera, Tomás; Vásquez A.E.; Kalergis Parra, Alexis Mikes© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to health bur-den. The worldwide economic and social impact of this virus is significant and must be addressed. The structural components of hMPV (either proteins or genetic material) can be detected by several receptors expressed by host cells through the engagement of pattern recognition receptors. The recognition of the structural components of hMPV can promote the signaling of the immune response to clear the infection, leading to the activation of several pathways, such as those related to the interferon response. Even so, several intrinsic factors are capable of modulating the immune response or directly inhibiting the replication of hMPV. This article will discuss the current knowledge regarding the innate and adaptive immune response during hMPV infections. Accordingly, the host intrinsic components capable of modulating the immune response and the elements capable of restricting viral replication during hMPV infections will be examined.
- ItemHuman metapneumovirus: mechanisms and molecular targets used by the virus to avoid the immune system(2018) Soto Ramírez, Jorge Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Benavente, Felipe; Pizarro Ortega, Magdalena S.; Lay, Margarita K.; Riedel, Claudia; Bueno Ramírez, Susan; González Muñoz, Pablo Alberto; Kalergis Parra, Alexis Mikes
- ItemInterim 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, CamilaThe 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.
- ItemSafety and immunogenicity evaluation of recombinant BCG vaccine against respiratory syncytial virus in a randomized, double-blind, placebo-controlled phase I clinical trial(2020) Abarca Villaseca, Katia; Rey Jurado, Emma; Muñoz Durango, Natalia; Soto Ramírez, Jorge Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Borzutzky Schachter, Arturo; Cerda, Jaime; Villarroel del Pino, Luis A.; González Muñoz, Pablo Alberto; González Aramundiz, José Vicente; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes; Valdés-Ferrada, J.; Iturriaga, C.; Urzúa, M.; Madrid, V.; Bueno Ramírez, Susan; Vázquez, Y.
- ItemSARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study(2022) Dib Marambio, Martín Javier; Le Corre Pérez, Monique Nicole; Ortiz Koh, Catalina Alejandra; García, Daniel; Ferrés, Marcela; Martínez Valdebenito, Constanza; Ruiz-Tagle, Cinthya; Ojeda Valenzuela, María José; Espinoza Sepúlveda, Manuel Antonio; Jara Contreras, Aquiles; Arab Verdugo, Juan Pablo; Rabagliati B., Ricardo; Vizcaya Altamirano, Cecilia; Ceballos, María Elena; Sarmiento Maldonado, Mauricio; Mondaca Contreras, Sebastián Patricio; Viñuela Morales, Macarena Rocío; Pastore Thomson, Antonia; Szwarcfiter Neiman, Vania; Galdames Lavín, Elizabeth Alejandra; Barrera Vásquez, Aldo Vincent; Castro Gálvez, Pablo Federico; Gálvez Arriagada, Nicolás Marcelo Salvador; Soto Ramírez, Jorge Andrés; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes; Nervi Nattero, Bruno; Balcells Marty, María ElviraSolid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster.