Browsing by Author "Andrade, Catalina A."

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    A molecular perspective for the development of antibodies against the human respiratory syncytial virus
    (2024) Loaiza, Ricardo A.; Ramirez, Robinson A.; Sepulveda-Alfaro, Javiera; Ramirez, Mario A.; Andrade, Catalina A.; Soto, Jorge A.; Gonzalez, Pablo A.; Bueno, Susan M.; Kalergis, Alexis M.
    The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.
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    Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults
    (2023) Pacheco, Gaspar A.; Andrade, Catalina A.; Galvez, Nicolas M. S.; Vazquez, Yaneisi; Rodriguez-Guilarte, Linmar; Abarca, Katia; Gonzalez, Pablo A.; Bueno, Susan M.; Kalergis, Alexis M.
    IntroductionThe human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples. MethodsPBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cell-derived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed. ResultsCompared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-& gamma;-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q. ConclusionImmunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals.
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    Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
    (2022) Galvez, Nicolas M. S.; Pacheco, Gaspar A.; Schultz, Barbara M.; Melo-Gonzalez, Felipe; Soto, Jorge A.; Duarte, Luisa F.; Gonzalez, Liliana A.; Rivera-Perez, Daniela; Rios, Mariana; Berrios, Roslye, V; Vazquez, Yaneisi; Moreno-Tapia, Daniela; Vallejos, Omar P.; Andrade, Catalina A.; Hoppe-Elsholz, Guillermo; Iturriaga, Carolina; Urzua, Marcela; Navarrete, Maria S.; Rojas, Alvaro; Fasce, Rodrigo; Fernandez, Jorge; Mora, Judith; Ramirez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Monica L.; Valiente-Echeverria, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; Gonzalez-Aramundiz, Jose, V; Johnson, Marina; Goldblatt, David; Gonzalez, Pablo A.; Abarca, Katia; Bueno, Susan M.; Kalergis, Alexis M.
    Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged & GE;18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-gamma and the expression of activation induced markers in CD4(+) T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-gamma secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule.
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    Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections
    (2020) Andrade, Catalina A.; Pacheco, Gaspar A.; Gálvez, Nicolas M. S.; Soto, Jorge A.; Bueno Ramírez, Susan; Kalergis, Alexis M.
    The human respiratory syncytial virus (hRSV) and human Metapneumovirus (hMPV) are two of the leading etiological agents of acute lower respiratory tract infections, which constitute the main cause of mortality in infants. However, there are currently approved vaccines for neither hRSV nor hMPV. Moreover, despite the similarity between the pathology caused by both viruses, the immune response elicited by the host is different in each case. In this review, we discuss how dendritic cells, alveolar macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid cells, and the complement system regulate both pathogenesis and the resolution of hRSV and hMPV infections. The roles that these cells play during infections by either of these viruses will help us to better understand the illnesses they cause. We also discuss several controversial findings, relative to some of these innate immune components. To better understand the inflammation in the lungs, the role of the respiratory epithelium in the recruitment of innate immune cells is briefly discussed. Finally, we review the main prophylactic strategies and current vaccine candidates against both hRSV and hMPV.
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    Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection
    (2021) Andrade, Catalina A.; Kalergis, Alexis; Bohmwald, Karen
    Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.