Browsing by Author "Soto Ramírez, Jorge Andrés"
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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.
- ItemCellular immune response induced by surface immunogenic protein with AbISCO-100 adjuvant vaccination decreases group B Streptococcus vaginal colonization(2019) Soto Ramírez, Jorge Andrés; Díaz Dinamarca, Diego A.; Soto, Daniel A.; Barrientos, Magaly J.; Carrión, Flavio; Kalergis Parra, Alexis Mikes; Vásquez, Abel E.
- ItemCholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic fux in skeletal muscle cells(2023) Abrigo, Johanna; Olguín Marín, Hugo César; Tacchi, Franco; Orozco-Aguilar, Josué; Valero-Breton, Mayalen; Soto Ramírez, Jorge Andrés; Castro-Sepúlveda, Mauricio; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, ClaudioBackground: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. Methods: We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. Results: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. Conclusion: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.
- ItemContribution of IDO to human respiratory syncytial virus infection(2019) Benavente, Felipe M.; Soto Ramírez, Jorge Andrés; Pizarro Ortega, Magdalena S.; Bohmwald Prieto, Karen; González, Pablo A.; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes
- ItemCurrent Insights in the Development of Efficacious Vaccines Against RSV(2020) Soto Ramírez, Jorge Andrés; Stephens, L. M.; Waldstein, K. A.; Canedo Marroquín, Gisela Eliana; Varga, S. M.; Kalergis Parra, Alexis Mikes
- ItemDifferent Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile(2023) Le Corre, Nicole; Abarca Villaseca, Katia; Astudillo, Patricio André; Potin Santander, Marcela Patricia; López, Sofía; Goldsack, Macarena; Valenzuela Guerrero, Vania; Schilling Redlich, Andrea; Gaete, Victoria; Rubio, Lilian; Calvo, Mario; Twele, Loreto; González, Marcela; Fuentes, Daniela; Gutiérrez Muñoz, Valentina José; Reyes Zaldivar, Felipe Tomás; Tapia, Lorena I.; Villena, Rodolfo; Retamal Díaz, Angello; Cárdenas, Antonio; Alarcón Bustamante, Eduardo; Xin, Qianqian; González Aramundiz, José Vicente; Álvarez Figueroa, María Javiera; González Muñoz, Pablo Alberto; Bueno Ramírez, Susan; Soto Ramírez, Jorge Andrés; Perret Pérez, Cecilia; Meng, Xing; Kalergis Parra, Alexis MikesDuring the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.
- 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
- ItemImmune responses during COVID-19 breakthrough cases in vaccinated children and adolescents(Frontiers Media SA, 2024) Rivera Pérez, Daniela; Méndez Vejar, Constanza Soledad; Diethelm Varela, Benjamín Manuel; Melo González, Felipe Andrés; Vázquez Hernández, Yaneisi; Meng, Xing; Xin, Qianqian; Fasce, Rodrigo A.; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Acevedo, Mónica L.; Valiente Echeverria, Fernando; Soto Rifo, Ricardo; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Astudillo Paredes, Patricio Andrés; Le Corre Pérez, Monique Nicole; Abarca Villaseca, Katia; Perret Pérez, Cecilia; González Muñoz, Pablo Alberto; Soto Ramírez, Jorge Andrés; Bueno Ramírez, Susan; Kalergis, Alexis M.Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260
- 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.
- ItemLung pathology due to hRSV infection impairs blood–brain barrier permeability enabling astrocyte infection and a long-lasting inflammation in the CNS(2021) Bohmwald Prieto, Karen; Soto Ramírez, Jorge Andrés; Andrade Parra, Catalina Andrea; Fernández Fierro, Ayleen Lorena; Espinoza Véliz, Janyra Alejandra; Rios Raggio, Mariana; Eugenin, E. A.; González Muñoz, Pablo Alberto; Opazo, M. C.; Kalergis Parra, Alexis Mikes
- 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.
- ItemThe humoral immune response induced by two recombinant bacillus Calmette-Guérin vaccines promotes viral clearance against the human respiratory sincytial virus and the human metapneumovirus in mice(2018) Soto Ramírez, Jorge Andrés; Kalergis Parra, Alexis Mikes; Pontificia Universidad Católica de Chile. Facultad de Ciencias BiológicasEl virus respiratorio sincicial humano (VRSh) y metapneumovirus humano (MPVh) son dos de los principales agentes etiológicos con mayor incidencia asociada a enfermedades respiratorias a nivel mundial, la incidencia de estos virus se ve incrementada durante las estaciones de otoño e invierno siendo principalmente VRSh el mayor causante de hospitalizaciones. Los principales reservorios de infección son recién nacidos, niños menores a dos años, personas inmunocomprometidas y ancianos. Los cuadros clínicos característicos asociados a la infección por estos virus son bronquitis y pneumonía. Sin embargo, se ha determinado que ambos virus podrían ser causantes de la aparición temprana de asma en niños. Además, se ha descrito que MPVh podría influenciar la aparición de enfermedades pulmonares obstructivas crónicas (EPOC). La patología asociada a la infección de estos virus es principalmente desencadenada por una respuesta inflamatoria caracterizada por un incremento en la secreción de citoquinas IL-4, IL-5, IL-8 acompañado de la producción de mucus en el epitelio pulmonar y a una contracción de las vías aéreas. Sumado a esto, la infección de ambos virus promueve a que la respuesta antiviral generada por la secreción de IFN de tipo I sea inhibida, esto, junto con una mala activación de los Linfocitos T, promueve un estado de anergia de estas células por parte de la infección mediada por VRSh desencadenado por la acumulación de proteína N del virus en la zona inducción de la sinapsis inmunológica, mientras que MPVh promueve que exista una baja activación de estas células asociado posiblemente a factores solubles, sin embargo, esto aún no ha sido comprobado. En la actualidad, no existen vacunas licenciadas para ninguno de estos virus. Sin embargo, algunos prototipos están siendo estudiados ya sea, en uso con animales como en pruebas en humanos. En nuestro laboratorio se generaron cepas recombinantes de la Mycobacteria Bacillus Calmette-Guérin (BCG) que expresan la proteína N-VRSh (rBCG-N) o la proteína P-MPVh (rBCG-P). Ambas vacunas fueron evaluadas en modelo animal encontrándose una respuesta inmune protectora a nivel celular mediado principalmente por la actividad de Linfocitos T. En este trabajo de tesis, se evaluó la respuesta inmune humoral inducida por estas vacunas y se logró determinar que ambas vacunas fueron capaces de promover la eliminación del agente viral, disminuyendo la inflamación pulmonar y parámetros asociados a infección. Además, se determinó que los anticuerpos secretados en respuesta a las vacunas tenían un perfil neutralizante y protector en modelo in vivo. Por otro lado, basados en la buena respuesta obtenida se decidió evaluar dos clones de la vacuna rBCG-P en condiciones de proceso de manufactura GMP y se evaluó el rol protector utilizando una dosis de inmunización menor a la usada anteriormente. Los resultados obtenidos permitieron concluir que la cepa rBCG-P clone 12 fue capaz de disminuir la inflamación pulmonar acompañada de una eficiente respuesta inmune humoral y celular vinculada a la activación de células T CD4+, CD8+, linfocitos B y una activa secreción de anticuerpos IgA e IgG. Finalmente, se determinó que la transferencia de anticuerpos y/o células provenientes de animales vacunados con esta cepa recombinante mostraron una eficiente eliminación del virus promoviéndose así una respuesta inmune protectora.