Frontiers in immunology
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Frontiers in immunology · Jan 2020
ReviewHigh-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects.
The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. ⋯ In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19.
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Frontiers in immunology · Jan 2020
ReviewProgress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines.
There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. ⋯ Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery.
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Frontiers in immunology · Jan 2020
ReviewAndrogen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung.
Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. ⋯ We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation.
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Frontiers in immunology · Jan 2020
ReviewHow to Combine the Two Landmark Treatment Methods-Allogeneic Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Together to Cure High-Risk B Cell Acute Lymphoblastic Leukemia?
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has made tremendous progress in the last few decades and is increasingly being used worldwide. The success of haploidentical HSCT has made it possible to have "a donor for everyone". Patients who received transplantation in remission may have a favorable outcome, while those who were transplanted in advanced stages of disease have a poor prognosis. ⋯ Therefore, combining these two approaches (allo-HSCT and CAR-T cell therapy) is an attractive area of research to further improve the prognosis of R/R B-ALL. In this review, we will discuss the current clinical practices of combining allo-HSCT with CAR-T cell therapy based on available data, including CAR-T cells as a bridge to allo-HSCT for R/R B-ALL and CAR-T cell infusion for post-transplant relapse. We will further explore not only other possible ways to combine the two approaches, including CAR-T cell therapy to clear minimal residual disease peri-transplantation and incorporation of CAR technology to treat graft-versus-host disease, but also the potential of CAR-T cells as a part of allo-HSCT.
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Frontiers in immunology · Jan 2020
ReviewRemodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response.
Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. ⋯ In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.