scholarly journals Role of Linker Length and Antigen Density in Nanoparticle Peptide Vaccine

ACS Omega ◽  
2019 ◽  
Vol 4 (3) ◽  
pp. 5547-5555 ◽  
Author(s):  
Chintan H. Kapadia ◽  
Shaomin Tian ◽  
Jillian L. Perry ◽  
J. Christopher Luft ◽  
Joseph M. DeSimone
2001 ◽  
Vol 226 (4) ◽  
pp. 307-311 ◽  
Author(s):  
James L. McAnally ◽  
Likang Xu ◽  
Matteo Villain ◽  
J. Edwin Blalock

Myasthenia gravis (MG) and its animal model, experimental autoimmune (EA) MG, are caused by interference with neuromuscular transmission by autoantibodies against the nicotinic acetylcholine receptor (AChR) on muscle. Previously, we have shown that two peptides, denoted RhCA 67-16 and RhCA 611-001, designed to be complementary in structure to the main immunogenic region and the dominant Lewis rat T cell epitope (α-chain residues 100-116) of the AChR, respectively, are effective vaccines that prevent EAMG in rats by inducing anti-idiotypic/clonotypic antibodies (Ab) and lowering levels of AChR Ab. These studies employed keyhole limpet hemocyanin (KLH) as a carrier and complete Freunds adjuvant (CFA). In advance of a clinical trial the present study tested the efficacy of RhCA 611-001 when combined with different adjuvants that are approved for use in humans. Adjuvants chosen for comparison were incomplete Freunds adjuvant (IFA) and aluminum hydroxide (Alum). As a second goal we evaluated diphtheria toxin (DT) as an alternative carrier protein to KLH. Alum was found to be an effective adjuvant, particularly when used with the peptide conjugated to DT. This combination of carrier and adjuvant provided protection against EAMG comparable with that observed with CFA and KLH. Using enzyme-linked immunosorbent assays for Ab against RhCA 611-001, it was found that disease protection is qualitatively, but not quantitatively, related to the anti-peptide Ab response. Our results demonstrate a vaccine formulation that should be useful in the first soon-to-be-conducted clinical trials of peptide vaccines to specifically correct aberrant T and B cell responses in an autoimmune disease.


2015 ◽  
Vol 3 (13) ◽  
pp. 2714-2724 ◽  
Author(s):  
Małgorzata Ferenc ◽  
Nadia Katir ◽  
Katarzyna Miłowska ◽  
Mosto Bousmina ◽  
Jean-Pierre Majoral ◽  
...  

Haemolytic activity and cellular toxicity of native, amino-, mercapto-, and carboxy-terminated SBA-15-type silicates were investigated.


2010 ◽  
Vol 269 (5) ◽  
pp. 546-556 ◽  
Author(s):  
M. Wigren ◽  
D. Kolbus ◽  
P. Dunér ◽  
I. Ljungcrantz ◽  
I. Söderberg ◽  
...  

2012 ◽  
Vol 51 (31) ◽  
pp. 7812-7816 ◽  
Author(s):  
Sarah-Jane Richards ◽  
Mathew W. Jones ◽  
Mark Hunaban ◽  
David M. Haddleton ◽  
Matthew I. Gibson

2020 ◽  
Vol 27 (17) ◽  
pp. 2887-2901 ◽  
Author(s):  
Stacey Bartlett ◽  
Mariusz Skwarczynski ◽  
Istvan Toth

Background: Innate immune system plays an important role in pathogen detection and the recognition of vaccines, mainly through pattern recognition receptors (PRRs) that identify pathogen components (danger signals). One of the typically recognised bacterial components are lipids in conjugation with peptides, proteins and saccharides. Lipidic compounds are readily recognised by the immune system, and thus are ideal candidates for peptide- based vaccine delivery. Thus, bacterial or synthetic lipids mixed with, or conjugated to, antigens have shown adjuvant properties. These systems have many advantages over traditional adjuvants, including low toxicity and good efficacy for stimulating mucosal and systemic immune responses. Methods: The most recent literature on the role of lipids in stimulation of immune responses was selected for this review. The vast majority of reviewed papers were published in the last decade. Older but significant findings are also cited. Results: This review focuses on the development of lipopeptide vaccine systems including application of palmitic acid, bacterial lipopeptides, glycolipids and the lipid core peptide and their routes of administration. The use of liposomes as a delivery system that incorporates lipopeptides is discussed. The review also includes a brief description of immune system in relation to vaccinology and discussion on vaccine delivery routes. Conclusion: Lipids and their conjugates are an ideal frontrunner in the development of safe and efficient vaccines for different immunisation routes.


2006 ◽  
Vol 119 (9) ◽  
pp. 740-748 ◽  
Author(s):  
Rui ZHANG ◽  
Pei-zeng YANG ◽  
Chang-you WU ◽  
Hao-li JIN ◽  
Bing LI ◽  
...  

2016 ◽  
Vol 53 (3) ◽  
pp. 224-232
Author(s):  
I. Christiana ◽  
R. Aparnaa ◽  
R. Rohit ◽  
D. Nageswara Rao ◽  
P. Kaliraj

SummaryFilarial thioredoxin and transglutaminase are enzymes that are secreted throughout the lifecycle of the parasites which are mandatory for the survival of the parasite. They are reported to be promising vaccine candidates, yet the limitation factors of these proteins to be developed as vaccines is their homology they share with the host proteins. Hence immunodominant epitopes from these proteins were constructed as peptides and immunised in mice model with Muramyl dipeptide (MDP) as adjuvant. Immunodominant epitopic portions from Filarial thioredoxin and transglutaminase which are non-homologous with host proteins were constructed as Multi Antigen Peptide (MAP) and assembled in an inert lysine core. The synthesised MAP was immunised with MDP as adjuvant in Balb/c mice model, humoral and cellular immune response were studied. Antibody titre levels for TT MAP with MDP was in par with alum as adjuvant in mice models. T cell responses of TT MAP with MDP showed a balanced TH1/TH2 response. The TH1 cytokines namely IL-2 and IFN-ɤ were also higher in TT MAP immunised groups with MDP as adjuvant whereas alum immunised groups was TH2 biased. TT MAP admixed with MDP as adjuvant proves to be safe in mice model. Further vaccination studies are underway in permissive animal models to determine the role of TT MAP with MDP as adjuvant in protective immunity againstW. bancroftiandB. malayiinfections.


2020 ◽  
Vol 401 (11) ◽  
pp. 1249-1255
Author(s):  
Ketaki D. Belsare ◽  
Anna Joëlle Ruff ◽  
Ronny Martinez ◽  
Ulrich Schwaneberg

AbstractCytochrome P450s are an important group of enzymes catalyzing hydroxylation, and epoxidations reactions. In this work we describe the characterization of the CinA–CinC fusion enzyme system of a previously reported P450 using genetically fused heme (CinA) and FMN (CinC) enzyme domains from Citrobacter braaki. We observed that mixing individually inactivated heme (-) with FMN (-) domain in the CinA-10aa linker - CinC fusion constructs results in recovered activity and the formation of (2S)-2β-hydroxy,1,8-cineole (174 µM), a similar amount when compared to the fully functional fusion protein (176 µM). We also studied the effect of the fusion linker length in the activity complementation assay. Our results suggests an intermolecular interaction between heme and FMN parts from different CinA–CinC fusion protein similar to proposed mechanisms for P450 BM3 on the other hand, linker length plays a crucial influence on the activity of the fusion constructs. However, complementation assays show that inactive constructs with shorter linker lengths have functional subunits, and that the lack of activity might be due to incorrect interaction between fused enzymes.


2012 ◽  
Vol 124 (31) ◽  
pp. 7932-7936 ◽  
Author(s):  
Sarah-Jane Richards ◽  
Mathew W. Jones ◽  
Mark Hunaban ◽  
David M. Haddleton ◽  
Matthew I. Gibson

2016 ◽  
Vol 69 (11-13) ◽  
pp. 1730-1747 ◽  
Author(s):  
Matthew L. Reback ◽  
Bojana Ginovska ◽  
Garry W. Buchko ◽  
Arnab Dutta ◽  
Nilusha Priyadarshani ◽  
...  

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