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1.
J Control Release ; 369: 556-572, 2024 May.
Article in English | MEDLINE | ID: mdl-38580136

ABSTRACT

Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (-1.18 mV) following encapsulation, referred to as n(OVA)C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8+ T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.


Subject(s)
Mice, Inbred C57BL , Ovalbumin , T-Lymphocytes, Cytotoxic , Animals , Ovalbumin/immunology , Ovalbumin/administration & dosage , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/drug effects , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemistry , Female , Methacrylates/chemistry , Polymers/chemistry , Polymers/administration & dosage , Nanoparticles/chemistry , Nanoparticles/administration & dosage , Mice , Vaccines/administration & dosage , Vaccines/immunology , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology , Nanovaccines
2.
Exp Ther Med ; 15(3): 2837-2843, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29456687

ABSTRACT

The present study explored the relationship between Girdin protein expression and the survival rate of patients with lung carcinoma. A total of 334 lung cancer specimens, 20 benign lung disease tissue sections and 24 fresh tissues from patients with lung carcinoma were analyzed by immunohistochemistry and western blotting. Girdin protein was expressed in 130/334 (38.93%) of the cases examined. Girdin protein expression was correlated with tumor/node/metastasis stage (P<0.001), lymph node metastasis (P=0.001), distant metastasis (P<0.001) and specimen sites (P=0.034). Girdin expression was also correlated with signal transducer and activator of transcription 3 (STAT3) expression (P<0.001). Patients with high Girdin and STAT3 expression had a significantly poorer prognosis compared with those with low/high, high/low or low/low expression (P<0.001). In summary, Girdin may be a prognostic marker of lung cancer and serve as a biomarker for metastasis.

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