Conformational HER-2/neuB-cell Epitope Peptide Vaccine Designed to Incorporate Two Native Disulfide Bonds Enhances Tumor Cell Binding and Antitumor Activities

The reduction of brain amyloid beta (Aβ) peptides by anti-Aβantibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβpeptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-Aβantibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβantibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42compared to Aβfibrils. The levels of serum anti-Aβantibodies and plasma Aβpeptides increased in both animals and decreased the brain Aβ40level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβantibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβpeptides and their toxic effects via clearance of Aβpeptides by generated antibodies.

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Structural features and functional domains of amassin-1, a cell-binding olfactomedin protein

Biochemistry and Cell Biology ◽

10.1139/o07-055 ◽

2007 ◽

Vol 85 (5) ◽

pp. 552-562 ◽

Cited By ~ 9

Author(s):

Brian J. Hillier ◽

Victor D. Vacquier

Keyword(s):

Disulfide Bonds ◽

Biological Activities ◽

Structural Features ◽

Body Cavity ◽

Binding Activity ◽

Coiled Coils ◽

Cell Binding ◽

Calcium Dependent ◽

Dependent Cell ◽

A Cell

Amassin-1 mediates a rapid cell adhesion that tightly adheres sea urchin coelomocytes (body cavity immunocytes) together. Three major structural regions exist in amassin-1: a short β region, 3 coiled coils, and an olfactomedin domain. Amassin-1 contains 8 disulfide-bonded cysteines that, upon reduction, render it inactive. Truncated forms of recombinant amassin-1 were expressed and purified from Pichia pastoris and their disulfide bonding and biological activities investigated. Expressed alone, the olfactomedin domain contained 2 intramolecular disulfide bonds, existed in a monomeric state, and inhibited amassin-1-mediated clotting of coelomocytes by a calcium-dependent cell-binding activity. The N-terminal β region, containing 3 cysteines, was not required for clotting activity. The coiled coils may dimerize amassin-1 in a parallel orientation through a homodimerizing disulfide bond. Neither amassin-1 fragments that were disulfide-linked as dimers or that were engineered to exist as dimers induced coelomocytes clotting. Clotting required higher multimeric states of amassin-1, possibly tetramers, which occurred through the N-terminal β region and (or) the first segment of coiled coils.

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Pentachlorophenol decreases tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells

Journal of Applied Toxicology ◽

10.1002/jat.1781 ◽

2011 ◽

Vol 32 (8) ◽

pp. 627-634 ◽

Cited By ~ 10

Author(s):

Tasia Hurd ◽

Jasmine Walker ◽

Margaret M. Whalen

Keyword(s):

Natural Killer Cells ◽

Cell Surface ◽

Protein Expression ◽

Tumor Cell ◽

Binding Capacity ◽

Surface Protein ◽

Cell Surface Protein ◽

Cell Binding ◽

Human Natural Killer Cells ◽

Surface Protein Expression

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The Role of Adjuvants in the Efficacy of a Peptide Vaccine for Myasthenia Gravis

Experimental Biology and Medicine ◽

10.1177/153537020122600407 ◽

2001 ◽

Vol 226 (4) ◽

pp. 307-311 ◽

Cited By ~ 8

Author(s):

James L. McAnally ◽

Likang Xu ◽

Matteo Villain ◽

J. Edwin Blalock

Keyword(s):

Myasthenia Gravis ◽

Peptide Vaccine ◽

Cell Epitope ◽

Keyhole Limpet Hemocyanin ◽

Peptide Vaccines ◽

Lewis Rat ◽

Cell Responses ◽

Immunogenic Region ◽

Experimental Autoimmune

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.

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A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

Breast Cancer Research and Treatment ◽

10.1007/s10549-009-0666-9 ◽

2009 ◽

Vol 119 (3) ◽

pp. 673-683 ◽

Cited By ~ 55

Author(s):

Ursula Wiedermann ◽

C. Wiltschke ◽

J. Jasinska ◽

M. Kundi ◽

R. Zurbriggen ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Immune Responses ◽

Phase I ◽

Phase I Study ◽

Peptide Vaccine ◽

Metastatic Breast ◽

Her 2

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Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.5939 ◽

2008 ◽

Vol 26 (6) ◽

pp. 897-906 ◽

Cited By ~ 82

Author(s):

Marta Guix ◽

Nara de Matos Granja ◽

Ingrid Meszoely ◽

Theresa B. Adkins ◽

Bobbye M. Wieman ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Tumor Cell ◽

Growth Factor Receptor ◽

Preoperative Treatment ◽

Breast Cancers ◽

Tumor Cell Proliferation ◽

Hormone Receptor Positive ◽

Er Positive ◽

Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

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12: Biomolecular Characterization for Development of a Peanut T‒Cell Epitope Peptide Therapy

Food Allergy ◽

10.1201/9781315120126-13 ◽

2017 ◽

pp. 351-372

Keyword(s):

T Cell ◽

Cell Epitope ◽

T Cell Epitope ◽

Epitope Peptide ◽

Peptide Therapy

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Development of a Trivalent Construct Omp18/AhpC/FlgH Multi Epitope Peptide Vaccine Against Campylobacter jejuni

Frontiers in Microbiology ◽

10.3389/fmicb.2021.773697 ◽

2022 ◽

Vol 12 ◽

Author(s):

Hongqiang Lou ◽

Xusheng Li ◽

Xiusheng Sheng ◽

Shuiqin Fang ◽

Shaoye Wan ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Tandem Repeats ◽

Expression System ◽

Peptide Vaccine ◽

Surface Protein ◽

Infection Model ◽

Protein Antigens ◽

Epitope Peptide ◽

Prokaryotic Expression System

Campylobacter jejuni (C. jejuni) is one of the major pathogens contributing to the enteritis in humans. Infection can lead to numerous complications, including but not limited to Guillain-Barre syndrome, reactive arthritis, and Reiter’s syndrome. Over the past two decades, joint efforts have been made toward developing a proper strategy of limiting the transmission of C. jejuni to humans. Nevertheless, except for biosecurity measures, no available vaccine has been developed so far. Judging from the research findings, Omp18, AhpC outer membrane protein, and FlgH flagellin subunits of C. jejuni could be adopted as surface protein antigens of C. jejuni for screening dominant epitope thanks to their strong antigenicity, expression of varying strains, and conservative sequence. In this study, bioinformatics technology was adopted to analyze the T-B antigenic epitopes of Omp18, AhpC, and FlgH in C. jejuni strain NCTC11168. Both ELISA and Western Blot methods were adopted to screen the dominant T-B combined epitope. GGS (GGCGGTAGC) sequence was adopted to connect the dominant T-B combined epitope peptides and to construct the prokaryotic expression system of tandem repeats of antigenic epitope peptides. The mouse infection model was adopted to assess the immunoprotective effect imposed by the trivalent T-B combined with antigen epitope peptide based on Omp18/AhpC/FlgH. In this study, a tandem epitope AhpC-2/Omp18-1/FlgH-1 was developed, which was composed of three epitopes and could effectively enhance the stability and antigenicity of the epitope while preserving its structure. The immunization of BALB/c mice with a tandem epitope could induce protective immunity accompanied by the generation of IgG2a antibody response through the in vitro synthesis of IFN-γ cytokines. Judging from the results of immune protection experiments, the colonization of C. jejuni declined to a significant extent, and it was expected that AhpC-2/Omp18-1/FlgH-1 could be adopted as a candidate antigen for genetic engineering vaccine of C. jejuni MAP.

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