Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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The roles of macrophage polarization in the host immune response to sepsis

International Immunopharmacology ◽

10.1016/j.intimp.2021.107791 ◽

2021 ◽

Vol 96 ◽

pp. 107791

Author(s):

Xinsen Chen ◽

Yancun Liu ◽

Yulei Gao ◽

Songtao Shou ◽

Yanfen Chai

Keyword(s):

Immune Response ◽

Macrophage Polarization ◽

Host Immune Response

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IKKβ-induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector

European Journal of Immunology ◽

10.1002/eji.201141910 ◽

2012 ◽

Vol 42 (3) ◽

pp. 681-687

Author(s):

Emily L. Hopewell ◽

Crystina C. Bronk ◽

Michael Massengill ◽

Robert W. Engelman ◽

Amer A. Beg

Keyword(s):

Immune Response ◽

Viral Vector

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Design of genetic construction for creation DNA vaccine against porcine reproductive and respiratory syndrome

Proceedings of the National Academy of Sciences of Belarus Biological Series ◽

10.29235/1029-8940-2018-63-4-419-425 ◽

2018 ◽

Vol 63 (4) ◽

pp. 419-425

Author(s):

L. M. Kravchenko ◽

K. V. Kudzin ◽

U. A. Prakulevich

Keyword(s):

Immune Response ◽

Dna Vaccine ◽

Mammalian Cells ◽

Dna Vaccines ◽

Viral Vector ◽

Signal Sequence ◽

Regulatory Elements ◽

Economic Damage ◽

Chain Gene ◽

Prrs Virus

The porcine reproductive and respiratory syndrome (PRRS) caused the serious economic damage to swine breeding around the world. It is a viral infective disease against which live attenuated and inactivated vaccines are not always successful. Development of new types of drugs such as DNA vaccines is necessary for improving the protection against the virus. DNA vaccines induce the development of both a cellular and humoral immune response. Such vaccines consist of a plasmid or viral vector with genes of potentially immunogenic proteins. The expression of these genes realized in cells of the vaccinated animal. It leads to the synthesis of antigen proteins triggering the immune response. The purpose of this work is to create a genetic construction that can be used as DNA vaccine against PRRS virus. The construction consists of the commercial vector pVAX1 and open reading frame of two structural proteins of PRRS virus, a lysosomal localization signal sequence of the invariant chain gene and regulatory elements necessary for the expression of cloned genes in mammalian cells.

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A folic acid-modified non-viral vector combines gene therapy with chemotherapy to reverse cancer chemotherapy resistance

Applied Materials Today ◽

10.1016/j.apmt.2021.101277 ◽

2021 ◽

pp. 101277

Author(s):

Jing Chen ◽

Wen Nie ◽

Yuzhu Hu ◽

Yangmei Shen ◽

Yunzhu Lin ◽

...

Keyword(s):

Gene Therapy ◽

Folic Acid ◽

Cancer Chemotherapy ◽

Viral Vector ◽

Chemotherapy Resistance

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Alternative Vaccination Routes against Paratuberculosis Modulate Local Immune Response and Interference with Tuberculosis Diagnosis in Laboratory Animal Models

Veterinary Sciences ◽

10.3390/vetsci7010007 ◽

2020 ◽

Vol 7 (1) ◽

pp. 7

Author(s):

Rakel Arrazuria ◽

Iraia Ladero ◽

Elena Molina ◽

Miguel Fuertes ◽

Ramón Juste ◽

...

Keyword(s):

Immune Response ◽

Macrophage Polarization ◽

Rabbit Model ◽

Cost Effective ◽

Effective Control ◽

Local Immune Response ◽

Skin Test Reactivity ◽

Tuberculosis Diagnosis ◽

Mycobacterium Avium Subsp Paratuberculosis ◽

Future Evaluation

Paratuberculosis (PTB) is an enteric granulomatous disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) that mainly affects ruminants. Current vaccines have shown to be cost–effective control reagents, although they are restricted due to cross-interference with bovine tuberculosis (bTB). Therefore, novel vaccination strategies are needed and this study is focused on evaluating alternative vaccination routes and their effect on the local immune response. The MAP oral challenge rabbit model was used to evaluate and compare an experimental inactivated MAP vaccine through oral (VOR) and intradermal (VID) routes. The VID group presented the highest proportion of animals with no visible lesions and the lowest proportion of animals with MAP positive tissues. Immunohistochemistry analysis revealed that the VID group presented a dominantly M1 polarized response indicating an ability to control MAP infection. In general, all vaccinated groups showed lower calprotectin levels compared to the non-vaccinated challenged group suggesting less active granulomatous lesions. The VID group showed some degree of skin test reactivity, whereas the same vaccine through oral administration was completely negative. These data show that PTB vaccination has an effect on macrophage polarization and that the route influences infection outcome and can also have an impact on bTB diagnosis. Future evaluation of new immunological products against mycobacterial diseases should consider assaying different vaccination routes.

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Caged siRNAs with single folic acid modification of antisense RNA for photomodulation of exogenous and endogenous gene expression in cells

Organic & Biomolecular Chemistry ◽

10.1039/c8ob01952e ◽

2018 ◽

Vol 16 (38) ◽

pp. 7029-7035 ◽

Cited By ~ 4

Author(s):

Lijia Yu ◽

Nannan Jing ◽

Zhenjun Yang ◽

Lihe Zhang ◽

Xinjing Tang

Keyword(s):

Gene Expression ◽

Folic Acid ◽

Complex Formation ◽

Antisense Rna ◽

Folate Receptor ◽

Acid Modification ◽

Endogenous Gene ◽

In Cells

Photoregulating gene expression using folic acid modified caged siRNA through complex formation of folic acid/folate receptor.

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Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

Nano-Micro Letters ◽

10.1007/s40820-020-00540-z ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Qin Zhao ◽

Miusi Shi ◽

Chengcheng Yin ◽

Zifan Zhao ◽

Jinglun Zhang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Immune Cells ◽

Inflammatory Responses ◽

Macrophage Polarization ◽

T Cell Response ◽

Dual Wavelength ◽

M2 Macrophage ◽

Adaptive Immune Responses ◽

Adaptive Immune

AbstractThe immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

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