This study aims to observe the tolerance and safety of recombinant adenovirus AIDS gag vaccine (Ad5-HIVgag) in adult HIV-infected patients receiving HAART treatment, in order to provide a safe dosing regimen for subsequent clinical trials; secondly, to gain a preliminary understanding of the immunogenicity of the vaccine.

Start Date-

Sponsor / Collaborator

National Institute for Viral Disease Control and Prevention, China CDC

100 Clinical Results associated with Ad5-HIVgag(National Institute for Viral Disease Control and Prevention, China CDC)

100 Translational Medicine associated with Ad5-HIVgag(National Institute for Viral Disease Control and Prevention, China CDC)

100 Patents (Medical) associated with Ad5-HIVgag(National Institute for Viral Disease Control and Prevention, China CDC)

Literatures (Medical) associated with Ad5-HIVgag(National Institute for Viral Disease Control and Prevention, China CDC)

01 Jan 2023·Frontiers in cellular and infection microbiology

Nipah virus attachment glycoprotein ectodomain delivered by type 5 adenovirus vector elicits broad immune response against NiV and HeV.

Article

Author: Wang, Shaoyan ; Zai, Xiaodong ; Xu, Junjie ; Wang, Shuyi ; Huang, Xiaoyan ; Zhang, Jun ; Li, Yaohui ; Yang, Lu ; Yin, Ying ; Li, Ruihua

Nipah virus (NiV) and Hendra virus (HeV) are newly emerging dangerous zoonotic pathogens of the Henipavirus genus of the Paramyxoviridae family. NiV and HeV (HNVs) which are transmitted by bats cause acute respiratory disease and fatal encephalitis in humans. To date, as there is a lack of antiviral drugs or effective antiviral therapies, the development of vaccines against those two viruses is of primary importance, and the immunogen design is crucial to the success of vaccines. In this study, the full-length protein (G), the ectodomain (Ge) and the head domain (Gs) of NiV attachment glycoprotein were delivered by the replication-defective type 5 adenovirus vector (Ad5) respectively, and the recombinant Ad5-NiV vaccine candidates (Ad5-NiVG, Ad5-NiVGe and Ad5-NiVGs) were constructed and their immunogenicity were evaluated in mice. The results showed that all the vaccine candidates stimulated specific humoral and cellular immune responses efficiently and rapidly against both NiV and HeV, and the Ad5-NiVGe elicited the strongest immune responses after a single-dose immunization. Furthermore, the potent conserved T-cell epitope DTLYFPAVGFL shared by NiV and HeV was identified in the study, which may provide valid information on the mechanism of HNVs-specific cellular immunity. In summary, this study demonstrates that the Ad5-NiVGe could be a potent vaccine candidate against HNVs by inducing robust humoral and cellular immune responses.

01 Sep 2018·Molecular Cancer TherapeuticsQ2 · MEDICINE

Leukocyte Differentiation by Histidine-Rich Glycoprotein/Stanniocalcin-2 Complex Regulates Murine Glioma Growth through Modulation of Antitumor Immunity

Q2 · MEDICINE

Article

Author: Claesson-Welsh, Lena ; Skare, Tor Persson ; Wollscheid, Bernd ; Noguer, Oriol ; Kaito, Hiroshi ; Pietilä, Ilkka ; Sobotzki, Nadine ; Essand, Magnus ; Roche, Francis P. ; Sjöström, Elisabet O. ; Welsh, Michael

AbstractThe plasma–protein histidine-rich glycoprotein (HRG) is implicated in phenotypic switching of tumor-associated macrophages, regulating cytokine production and phagocytotic activity, thereby promoting vessel normalization and antitumor immune responses. To assess the therapeutic effect of HRG gene delivery on CNS tumors, we used adenovirus-encoded HRG to treat mouse intracranial GL261 glioma. Delivery of Ad5-HRG to the tumor site resulted in a significant reduction in glioma growth, associated with increased vessel perfusion and increased CD45+ leukocyte and CD8+ T-cell accumulation in the tumor. Antibody-mediated neutralization of colony-stimulating factor-1 suppressed the effects of HRG on CD45+ and CD8+ infiltration. Using a novel protein interaction–decoding technology, TRICEPS-based ligand receptor capture (LRC), we identified Stanniocalcin-2 (STC2) as an interacting partner of HRG on the surface of inflammatory cells in vitro and colocalization of HRG and STC2 in gliomas. HRG reduced the suppressive effects of STC2 on monocyte CD14+ differentiation and STC2-regulated immune response pathways. In consequence, Ad5-HRG–treated gliomas displayed decreased numbers of IL35+ Treg cells, providing a mechanistic rationale for the reduction in GL261 growth in response to Ad5-HRG delivery. We conclude that HRG suppresses glioma growth by modulating tumor inflammation through monocyte infiltration and differentiation. Moreover, HRG acts to balance the regulatory effects of its partner, STC2, on inflammation and innate and/or acquired immunity. HRG gene delivery therefore offers a potential therapeutic strategy to control antitumor immunity. Mol Cancer Ther; 17(9); 1961–72. ©2018 AACR.

01 Apr 2018·Journal of Molecular MedicineQ2 · MEDICINE

Immunization with an adenovirus-vectored TB vaccine containing Ag85A-Mtb32 effectively alleviates allergic asthma

Q2 · MEDICINE

Article

Author: Wang, Qian ; Ye, Xianmiao ; Li, Chufang ; Wang, Jinlin ; Sun, Baoqing ; Li, Feng ; Zhang, Yiling ; Feng, Ying ; Li, Liang ; Zhong, Nanshan ; Li, Pingchao ; Chen, Ling ; Zheng, Xuehua ; Feng, Liqiang ; Li, Na ; Gao, Xiang ; Su, Zhong ; Lai, Kefang

Current treatments for allergic asthma primarily ameliorate symptoms rather than inhibit disease progression. Regulating the excessive T helper type 2 (Th2) responses may prevent asthma exacerbation. In this study, we investigated the protective effects of Ad5-gsgAM, an adenovirus vector carrying two mycobacterial antigens Ag85A and Mtb32, against allergic asthma. Using an ovalbumin (OVA)-induced asthmatic mouse model, we found that Ad5-gsgAM elicited much more Th1-biased CD4⁺T and CD8⁺T cells than bacillus Calmette-Guérin (BCG). After OVA challenge, Ad5-gsgAM-immunized mice showed significantly lowered airway inflammation in comparison with mice immunized with or without BCG. Total serum immunoglobulin E and pulmonary inducible-nitric-oxide-synthase were efficiently reduced. The cytokine profiles in bronchial-alveolar-lavage-fluids (BALFs) were also modulated, as evidenced by the increased level of interferon-γ (IFN-γ) and the decreased level of interleukin (IL)-4, IL-5, and IL-13. Anti-inflammatory cytokine IL-10 was sharply increased, whereas pro-inflammatory cytokine IL-33 was significantly decreased. Importantly, exogenous IL-33 abrogated the protective effects of Ad5-gsgAM, revealing that the suppression of IL-33/ST2 axis substantially contributed to protection against allergic inflammation. Moreover, regulatory T cells were essential for regulating aberrant Th2 responses as well as IL-33/ST2 axis. These results suggested that modulating the IL-33/ST2 axis via adenovirus-vectored mycobacterial antigen vaccination may provide clinical benefits in allergic inflammatory airways disease.KEY MESSAGES•Ad5-gsgAM elicits Th1 responses and suppresses Th2-mediated allergic asthma in mice. •Ad5-gsgAM inhibits IL-33/ST2 axis by reducing IL-33 secretion but not ILC2 recruiting. •Treg is essential for modulating Th2 responses and IL-33/ST2 axis by Ad5-gsgAM.

100 Deals associated with Ad5-HIVgag(National Institute for Viral Disease Control and Prevention, China CDC)

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Indication	Highest Phase	Country/Location	Organization	Date
Acquired Immunodeficiency Syndrome	Phase 1	CN	National Institute for Viral Disease Control and Prevention, China CDC	30 Mar 2016

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