Jianqi Wu

Bio: Jianqi Wu is an academic researcher from Harbin Medical University. The author has contributed to research in topics: Medicine & Tumor microenvironment. The author has an hindex of 4, co-authored 5 publications receiving 117 citations.

Oral vaccination with a liposome‐encapsulated influenza DNA vaccine protects mice against respiratory challenge infection

Abstract: It is well accepted that vaccination by oral administration has many advantages over injected parenteral immunization. The present study focuses on whether oral vaccination with a DNA vaccine could induce protective immunity against respiratory challenge infection. The M1 gene of influenza A virus was used to construct DNA vaccine using pcDNA 3.1(+) plasmid, a eukaryotic expression vector. The cationic liposomes were used to deliver the constructed DNA vaccine. In vitro and in vivo expression of M1 gene was observed in the cell line and in the intestine of orally vaccinated C57BL/6 mice, respectively. It became clear that this type of oral DNA vaccination was capable of inducing both humoral and cellular immune responses, together with an augmentation of IFN-γ production. In addition, oral vaccination with liposome-encapsulated DNA vaccine could protect the mice against respiratory challenge infection. These results suggest that gastrointestinal tract, a constituent member of the common mucosal immune system, is a potent candidate applicable as a DNA vaccine route against virus respiratory diseases.

IL-33 Receptor (ST2) Signalling is Important for Regulation of Th2-Mediated Airway Inflammation in a Murine Model of Acute Respiratory Syncytial Virus Infection.

Abstract: T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is the ligand-binding component of the receptor for the cytokine IL-33, a newly identified cytokine known to amplify the Th2 cell-dominant immune responses. The function of IL-33/ST2 signalling during respiratory syncytial virus (RSV) infection is not fully known. In this study, following intranasal infection with RSV, BALB/c mice showed a marked increase in the production of IL-33, with an elevated expression of ST2 mRNA as well as a massive infiltration of CD45(+) ST2(+) cells in the lungs, suggesting that during the early phase of RSV infection, IL-33 target cells which express ST2 on cell surface, may play a critical role for the development of RSV-induced airway inflammation. Indeed, blocking ST2 signalling using anti-ST2 monoclonal antibody diminished not only RSV-induced eosinophil recruitment, but also the amounts of Th2-associated cytokines, particularly IL-13, and Th17-type cytokine IL-17A in the lungs of infected mice. However, anti-ST2 antibody treatment did not affect the production of Th1-type cytokine IFN-γ as well as pulmonary viral growth and clearance. These results indicate that IL-33/ST2 signalling is involved in RSV-induced, Th2-associated airway inflammation but not protective immunity.

Ferroptosis, as the most enriched programmed cell death process in glioma, induces immunosuppression and immunotherapy resistance.

Abstract: BACKGROUND Immunosuppressive microenvironment is a major cause of immunotherapeutic resistance in glioma. In addition to secreting compounds, tumor cells under programmed cell death (PCD) processes release abundant mediators to modify the neighboring microenvironment. However, the complex relationship among PCD status, immunosuppressive microenvironment and immunotherapy is still poorly understood. METHODS Four independent glioma cohorts comprising 1,750 patients were enrolled for analysis. The relationships among PCD status, microenvironment cellular components and biological phenotypes were fully explored. Tissues from our hospital and experiments in vitro and in vivo were used to confirm the role of ferroptosis in glioma. RESULTS Analyses to determine enriched PCD processes showed that ferroptosis was the main type of PCD in glioma. Enriched ferroptosis correlated with progressive malignancy, poor outcomes and aggravated immunosuppression in glioblastoma (GBM) patients. Enhanced ferroptosis was shown to induce activation and infiltration of immune cells but attenuated antitumor cytotoxic killing. Tumor-associated macrophages (TAMs) were found to participate in ferroptosis-mediated immunosuppression. Preclinically, ferroptosis inhibition combined with PD-1/L1 blockade generated a synergistic therapeutic outcome in GBM murine models. CONCLUSIONS This work provides a molecular, clinical and biological landscape of ferroptosis, suggesting a role of ferroptosis in glioma malignancy and a novel synergic immunotherapeutic strategy that combines immune checkpoint blockade (ICB) treatment with ferroptosis inhibition.

Respiratory syncytial virus protects against the subsequent development of ovalbumin‐induced allergic responses by inhibiting Th2‐type γδ T cells

Abstract: Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans still remain inconclusive. The association between RSV infection and allergic diseases may be dependent on an atopic background and previous history of RSV infection. It has been reported that RSV infection before sensitization to an allergen decreased the production of Th2-like cytokines in the lung and the levels of allergen-specific Th2-type antibodies in the serum. However, the underlying mechanisms are largely unknown. In the present study, the role of pulmonary γδ T cells in RSV-affected, allergen-induced airway inflammation was investigated. BALB/c mice were sensitized to or challenged with ovalbumin (OVA) and infected with RSV either before or after the sensitization period. It became clear that sensitization and challenge of mice with OVA induced a large influx of γδ T cells to the lungs. However, prior RSV infection inhibited the infiltration of γδ T cells as well as activated γδ T cells, characterized by expression of CD40L or CD69 molecular in the cell surface. Moreover, prior RSV infection elevated the type 1 cytokine gene expression but suppressed type 2 cytokine expression in the lung γδ T cells. Adoptive transfer of γδ T cells from OVA-sensitized and challenged mice increased airway inflammation, suggesting that γδ T cells may play a proinflammatory role in allergic responses. These results described here support the idea of an unknown γδ T cell-dependent mechanism in the regulation of RSV-affected, allergen-induced allergic airway responses. J. Med. Virol. 85:149–156, 2012. © 2012 Wiley Periodicals, Inc.

Liposomes as vaccine delivery systems: a review of the recent advances

Abstract: Liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems in vaccine development and the interest for liposome-based vaccines has markedly...

Molecular mechanisms for enhanced DNA vaccine immunogenicity

Abstract: In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.

Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity

Abstract: A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but have not achieved widespread acceptance for use in humans due to their low immunogenicity in early clinical studies. However, recent clinical data have re-established the value of DNA vaccines, particularly in priming high-level antigen-specific antibody responses. Several approaches have been investigated for improving DNA vaccine efficacy, including advancements in DNA vaccine vector design, the inclusion of genetically engineered cytokine adjuvants, and novel non-mechanical delivery methods. These strategies have shown promise, resulting in augmented adaptive immune responses in not only mice, but also in large animal models. Here, we review advancements in each of these areas that show promise for increasing the immunogenicity of DNA vaccines.