Browsing by Author "Peñaloza, H.F."

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    Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults
    (2022) Melo González, Felipe; Méndez, Constanza; Peñaloza, H.F.; Schultz, B.M.; Piña Iturbe, A.; Ríos, M.; Moreno Tapia, D.; Pereira Sánchez, P.; Leighton, D.; Orellana, C.; Covarrubias, C.; Gálvez, N.M.S.; Soto, J.A.; Duarte, L.F.; Rivera Pérez, D.; Vázquez, Y.; Cabrera, A.; Bustos, S.; Iturriaga, C.; Urzua, M.; Navarrete, M.S.; Rojas, Á.; Fasce, R.; Fernández, J.; Mora, J.; Ramírez, E.; Gaete Argel, A.; Acevedo, M.; Valiente Echeverría, F.; Soto Rifo, R.; Weiskopf, D.; Grifoni, A.; Sette, A.; Zeng, G.; Meng, W.; González Aramundiz, J.V.; González, P.A.; Abarca, K.; Bueno, S.M.; Kalergis, A.M.
    The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 pandemic even in highly vaccinated countries. While a second booster of mRNA vaccines improved the immunity against SARS-CoV-2, the humoral and cellular responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac® increased the neutralizing response against the ancestral virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ T cells and IFN-γ production when stimulated with a mega-pool of peptides derived from the spike protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac® does not improve the neutralizing response against the Omicron variant compared with the first booster dose, yet it helps maintaining a robust spike-specific CD4+ T cell response.
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    L-Arginine Enhances Intracellular Killing of Carbapenem-Resistant Klebsiella pneumoniae ST258 by Murine Neutrophils
    (2020) Peñaloza, H.F.; Ahn, D.; Schultz, B.M.; Piña-Iturbe, A.; González, L.A.; Bueno, S.M.
    Carbapenem-resistant Klebsiella pneumoniae ST258 (CRKP-ST258) are a global concern due to their rapid dissemination, high lethality, antibiotic resistance and resistance to components of the immune response, such as neutrophils. Neutrophils are major host mediators, able to kill well-studied and antibiotic-sensitive laboratory reference strains of K. pneumoniae. However, CRKP-ST258 are able to evade neutrophil phagocytic killing, persisting longer in the host despite robust neutrophil recruitment. Here, we show that neutrophils are unable to clear a CRKP-ST258 isolate (KP35). Compared to the response elicited by a prototypic K. pneumoniae ATCC 43816 (KPPR1), the neutrophil intracellular response against KP35 is characterized by equivalent production of reactive oxygen species (ROS) and myeloperoxidase content, but impaired phagosomal acidification. Our results ruled out that this phenomenon is due to a phagocytosis defect, as we observed similar efficiency of phagocytosis by neutrophils infected with KP35 or KPPR1. Genomic analysis of the cps loci of KPPR1 and KP35 suggest that the capsule composition of KP35 explain the high phagocytosis efficiency by neutrophils. Consistent with other reports, we show that KP35 did not induce DNA release by neutrophils and KPPR1 only induced it at 3 h, when most of the bacteria have already been cleared. l-arginine metabolism has been identified as an important modulator of the host immune response and positively regulate T cells, macrophages and neutrophils in response to microbes. Our data show that l-arginine supplementation improved phagosome acidification, increased ROS production and enhanced nitric oxide consumption by neutrophils in response to KP35. The enhanced intracellular response observed after l-arginine supplementation ultimately improved KP35 clearance in vitro. KP35 was able to dysregulate the intracellular microbicidal machinery of neutrophils to survive in the intracellular environment. This process, however, can be reversed after l-arginine supplementation.