scholarly journals Harnessing the Activation of Toll-Like Receptor 2/6 by Self-Assembled Cross-β Fibrils to Design Adjuvanted Nanovaccines

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1981 ◽  
Author(s):  
Soultan Al-Halifa ◽  
Ximena Zottig ◽  
Margaryta Babych ◽  
Mélanie Côté-Cyr ◽  
Steve Bourgault ◽  
...  

Protein fibrils characterized with a cross-β-sheet quaternary structure have gained interest as nanomaterials in biomedicine, including in the design of subunit vaccines. Recent studies have shown that by conjugating an antigenic determinant to a self-assembling β-peptide, the resulting supramolecular assemblies act as an antigen delivery system that potentiates the epitope-specific immune response. In this study, we used a ten-mer self-assembling sequence (I10) derived from an amyloidogenic peptide to biophysically and immunologically characterize a nanofibril-based vaccine against the influenza virus. The highly conserved epitope from the ectodomain of the matrix protein 2 (M2e) was elongated at the N-terminus of I10 by solid phase peptide synthesis. The chimeric M2e-I10 peptide readily self-assembled into unbranched, long, and twisted fibrils with a diameter between five and eight nm. These cross-β nanoassemblies were cytocompatible and activated the heterodimeric Toll-like receptor (TLR) 2/6. Upon mice subcutaneous immunization, M2e-fibrils triggered a robust anti-M2e specific immune response, which was dependent on self-assembly and did not require the use of an adjuvant. Overall, this study describes the efficacy of cross-β fibrils to activate the TLR 2/6 and to stimulate the epitope-specific immune response, supporting usage of these proteinaceous assemblies as a self-adjuvanted delivery system for antigens.

2019 ◽  
Vol Volume 14 ◽  
pp. 4867-4880 ◽  
Author(s):  
Pritsana Sawutdeechaikul ◽  
Banphot Jiangchareon ◽  
Supason Wanichwecharungruang ◽  
Tanapat Palaga

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1290
Author(s):  
Hoang-Thanh Le ◽  
Nya L. Fraleigh ◽  
Jordan D. Lewicky ◽  
Justin Boudreau ◽  
Paul Dolinar ◽  
...  

The addictive nature of nicotine is likely the most significant reason for the continued prevalence of tobacco smoking despite the widespread reports of its negative health effects. Nicotine vaccines are an alternative to the currently available smoking cessation treatments, which have limited efficacy. However, the nicotine hapten is non-immunogenic, and successful vaccine formulations to treat nicotine addiction require both effective adjuvants and delivery systems. The immunomodulatory properties of short, non-natural peptide sequences not found in human systems and their ability to improve vaccine efficacy continue to be reported. The aim of this study was to determine if small “non-natural peptides,” as part of a conjugate nicotine vaccine, could improve immune responses. Four peptides were synthesized via solid phase methodology, purified, and characterized. Ex vivo plasma stability studies using RP-HPLC confirmed that the peptides were not subject to proteolytic degradation. The peptides were formulated into conjugate nicotine vaccine candidates along with a bacterial derived adjuvant vaccine delivery system and chitosan as a stabilizing compound. Formulations were tested in vitro in a dendritic cell line to determine the combination that would elicit the greatest 1L-1β response using ELISAs. Three of the peptides were able to enhance the cytokine response above that induced by the adjuvant delivery system alone. In vivo vaccination studies in BALB/c mice demonstrated that the best immune response, as measured by nicotine-specific antibody levels, was elicited from the conjugate vaccine structure, which included the peptide, as well as the other components. Isotype analyses highlighted that the peptide was able to shift immune response toward being more humorally dominant. Overall, the results have implications for the use of non-natural peptides as adjuvants not only for the development of a nicotine vaccine but also for use with other addictive substances and conventional vaccination targets as well.


2016 ◽  
Vol 8 (30) ◽  
pp. 19276-19283 ◽  
Author(s):  
Jie Xing ◽  
Zhenguang Liu ◽  
Yifan Huang ◽  
Tao Qin ◽  
Ruonan Bo ◽  
...  

2019 ◽  
Vol 21 (2) ◽  
pp. 621-629 ◽  
Author(s):  
Risako Miura ◽  
Shin-ichi Sawada ◽  
Sada-atsu Mukai ◽  
Yoshihiro Sasaki ◽  
Kazunari Akiyoshi

2021 ◽  
Author(s):  
Kannaki T Ramasamy ◽  
E Priyanka ◽  
Manda Abhilash ◽  
Santosh Haunshi

Abstract Toll-like receptor (TLR) agonists are emerging as promising vaccine adjuvants and immunomodulators in poultry against many diseases. Infectious bursa disease (IBD) still remains as a major threat in poultry industry. Improving the vaccine mediated immune response would help in better protection against IBD virus infection. Adjuvant potential of TLR3 agonist, Poly I:C with different IBD vaccines has been analyzed in chicken in the present study. Intermediate, intermediate plus IBD vaccine, bursaplex vaccine and their respective poly I:C combinations were used for immunization of chicken. IBD specific antibody titre, bursa to body weight ratio, body weight gain and bursal lesion scores were evaluated at weekly interval in different immunization groups. Fold changes in cytokines IL-1β and IFN-γ mRNA expression levels were also analyzed in different groups. Intermediate IBD plus vaccine induced significantly (P≤0.05) higher IBD specific antibody response at 35 days of age than other groups with comparatively lower body weight gain and moderate bursal lesion score. Poly I:C co-administration with intermediate IBD vaccine and bursaplex vaccine improved the IBD specific antibody titres, better body weight gain and moderately less bursal lesion score. However, Poly I:C combination with intermediate plus IBD vaccine did not improve the specific immune response. IL-1β levels were up-regulated in intermediate plus and bursaplex group, whereas IFN-γ m RNA expression levels were upregulated in intermediate IBD with Poly IC group. In conclusion, poly I:C co-administration with intermediate IBD and bursaplex vaccine was beneficial and improved the specific immune response with least immunosuppression and bursal damage.


2015 ◽  
Vol 1 (1) ◽  
pp. 23
Author(s):  
Niken Ulupi ◽  
Muhammad Amrullah Pagala

ABSTRAK Gen Toll-like Receptor 4 (TLR4) adalah salah satu gen yang mengontrol ketahanan ayam terhadap serangan Salmonella sp, melalui respon immun non-specific. Gen ini dapat digunakan sebagai marka genetik pada ayam.  Oleh karena itu penelitian ini bertujuan mengevaluasi polimorfisme genetik gen TLR4 pada beberapa jenis ayam (Ayam Tolaki, Ayam Ras pedaging dan petelur). Total sampel sebanyak 126. Penelitian ini melalui 3 tahapan yakni ekstraksi DNA, amplifikasi PCR (dengan ukuran DNA 220 pb pada ekson 2), dan metode RFLP menggunakan  enzim MscI.  Hasil penelitian menunjukkan gen TLR4 | MscI bersifat polimorfik pada semua jenis ayam. Diperoleh 2 alel (A dan G). Frekuensi alel G (membawa sfat resisten) pada ayam Tolaki, Ras pedaging, dan petelur masing-masing 0.77, 0.87 dan 0.20. Nilaix2menunjukkan genTLR4|MscI berada dalan keseimbangan Hardy-Weinberg dengan Ho dan He 0,31 dan 0,29. Nilai PIC 0,25 termasuk kategori medium. Gen TLR4| MscI dapat digunakan sebagai marka genetik sifat ketahanan ayam Tolaki terhadap infeksi Salmonellasp.   Keywords : Polimorfik, Gen TLR4, Salmonella sp., Non-Specific Immune Response


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