A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally

2021 ◽  
pp. 105335
Author(s):  
Xiufen Du ◽  
Daquan Tan ◽  
Yang Gong ◽  
Yifan Zhang ◽  
Jiangyuan Han ◽  
...  
2009 ◽  
Vol 75 (24) ◽  
pp. 7739-7744 ◽  
Author(s):  
Natalie A. Parlane ◽  
D. Neil Wedlock ◽  
Bryce M. Buddle ◽  
Bernd H. A. Rehm

ABSTRACT Bioengineered bacterial polyester inclusions have the potential to be used as a vaccine delivery system. The biopolyester beads were engineered to display a fusion protein of the polyester synthase PhaC and the two key antigens involved in immune response to the infectious agent that causes tuberculosis, Mycobacterium tuberculosis, notably antigen 85A (Ag85A) and the 6-kDa early secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis. Polyester beads displaying the respective fusion protein at a high density were successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity to the displayed antigens was investigated. The beads were not toxic to the animals, as determined by weight gain and absence of lesions at the inoculation site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice induced significant humoral and cell-mediated immune responses to both Ag85A and ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity on their own, and this ability was enhanced by administration of the beads in an oil-in-water emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads induced significantly stronger humoral and cell-mediated immune responses than vaccination with an equivalent dose of the fusion protein Ag85A-ESAT-6 alone. The immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed from the induction of the cytokine gamma interferon (Th1 immune response) and increased levels of immunoglobulin G1 (Th2 immune response). Hence, engineered biopolyester beads displaying foreign antigens represent a new class of versatile, safe, and biocompatible vaccines.


2021 ◽  
Author(s):  
Arshid Yousefi Avarvand ◽  
Zahra Meshkat ◽  
Farzad Khademi ◽  
Ehsan Aryan ◽  
Mojtaba Sankian ◽  
...  

Background: Tuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new tuberculosis vaccines could enhance the immunogenicity of M. tuberculosis antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through the intranasal administration in mice model. Methods:In present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of 2 weeks. Finally, IFN-γ, IL-4. IL-17 and TGF-β concentration in supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG1 and IgG2a and sIgA titers in nasal lavage were determined. Results:According to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induced IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of M. tuberculosis antigens. Conclusion: The results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM and MPLA after nasal administration in enhancing immune response against of M. tuberculosis antigens. So, nasal immunization with these formulations, could induce immune responses and considered as new TB vaccine or as BCG booster.


2020 ◽  
Vol 17 ◽  
Author(s):  
Mohsen Sisakht ◽  
Amir Mahmoodzadeh ◽  
Mohammadsaeid Zahedi ◽  
Davood Rostamzadeh ◽  
Amin Moradi Hasan-Abad ◽  
...  

Background: Human papillomavirus (HPV) is the main biological agent causing sexually transmitted diseases (STDs), including precancerous lesions and several types of prevalent cancers. To date, numerous types of vaccines are designed to prevent high-risk HPV. However, their prophylactic effect is not the same and does not clear previous infections. Therefore, there is an urgent need for developing therapeutic vaccines that trigger cell-mediated immune responses for the treatment of HPV. The HPV16 E6 and E7 proteins are ideal targets for vaccine therapy against HPV. Fusion protein vaccines, which include both immunogenic interest protein and an adjuvant for augmenting the immunogenicity effects, are theoretically capable of guarantee the power of the immune system against HPV. Method: A vaccine construct, including HPV16 E6/E7 proteins along with a heat shock protein GP96 (E6/E7-NTGP96 construct), was designed using in silico methods. By the aid of the SWISS-MODEL server, the optimal 3D model of the designed vaccine was selected, followed by physicochemical and molecular parameters were performed using bioinformatics tools. Docking studies were done to evaluate the binding interaction of the vaccine. Allergenicity, immunogenicity, B, and T cell epitopes of the designed construct were predicted. Results: Immunological and structural computational results illustrated that our designed construct is potentially proper for stimulation of cellular and humoral immune responses against HPV. Conclusion: Computational studies showed that the E6/E7-NTGP96 construct is a promising candidate vaccine that needs further in vitro and in vivo evaluations.


2019 ◽  
Vol 129 ◽  
pp. 68-73 ◽  
Author(s):  
Mohsen Karbalaei Zadeh Babaki ◽  
Mahboubeh Taghiabadi ◽  
Saman Soleimanpour ◽  
Masoud Saleh Moghadam ◽  
Arman Mosavat ◽  
...  

2011 ◽  
Vol 44 (13) ◽  
pp. S46
Author(s):  
Elham Mohit ◽  
Azam Bolhassani ◽  
Farnaz Zahedifard ◽  
Mohammad Taghikhani ◽  
Eslamifar Ali ◽  
...  

2015 ◽  
Vol 95 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Xiu-qin Yang ◽  
Liang Wang ◽  
Hai-tao Li ◽  
Di Liu

Yang, X.-q., Wang, L., Li, H.-t. and Liu, D. 2015. Immune responses of porcine airway epithelial cells to poly(I:C), a synthetic analogue of viral double-stranded RNA. Can. J. Anim. Sci. 95: 13–20. Swine respiratory disease (SRD) is one of the most economically important diseases affecting the pig industry. The main infectious agents that cause SRD are viruses, but the molecular pathogenesis of viral SRD has not been extensively studied. Here, using digital gene expression tag profiling, the global transcriptional responses to poly(I:C), a synthetic analogue of viral double-stranded RNA, was analyzed in porcine airway epithelial cells (PAECs). The profiling analysis revealed numerous differentially expressed genes (DEGs), including unknown sequences in the porcine nucleotide databases. Gene ontology enrichment analysis showed that DEGs were mainly enriched in response to stress (GO: 0006950), of which, defense response is one sub-process. Poly(I:C) challenge induced a general inflammation response as indicated by marked upregulation of a variety of pathogen recognition receptors, interferon-stimulated genes, proinflammatory cytokines, and chemokines, together with the significant downregulation of anti-inflammatory molecules. Furthermore, the antiapoptotic pathway was triggered, as demonstrated by the significant suppression of molecules involved in the induction of apoptosis, together with the significant stimulation of putative inhibitor of apoptosis. The results indicate that PAECs initiated defense against poly(I:C) challenge through the inflammation responses, whereas poly(I:C) can utilize antiapoptotic pathway to evade host defense.


2015 ◽  
Vol 44 (5) ◽  
pp. 482-496 ◽  
Author(s):  
Jingcai Lu ◽  
Tianxu Sun ◽  
Dandan Wang ◽  
Yunliang Dong ◽  
Man Xu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document