Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis

Kovjazin, Riva; Shitrit, David; Preiss, Rachel; Haim, Ilanit; Triezer, Lev; Fuks, Leonardo; Nader, Abdel Rahman; Raz, Meir; Bardenstein, Ritta; Horn, Galit; Smorodinsky, Nechama I.; Carmon, Lior

doi:10.1128/cvi.00586-12

Cited by 10 publications

(17 citation statements)

References 40 publications

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“…Furthermore, T-cell lines induced ex-vivo against these SP domains, using both naive and patient-derived PBMCs, demonstrated an effector memory profile (CD45RO C CD44 C CD62L high ), coupled with robust antigenspecific IFN-g production, as well as cytotoxic properties against MUC1-positive tumor 45 and MTb-infected cells. 46 Similarly, these SP domains induced a strong and specific cellular immune response [45][46][47] and anti-tumor activity 45 in both mice and in a firstin-human study. 48 More recently, an additional support for the potency of SP domains was published by Kerzerho et al, which demonstrated the existence of multiple CD4…”

Section: Antigen-specific Cd4mentioning

confidence: 97%

“…3). 45,46 As SP domains preferably bind human MHC alleles, initial bio-validation of the selected SP domains and controlled antigen match peptides, is performed in-vitro on large sample pools of peripheral blood mononuclear cell (PBMC) obtained from both na€ ıve and disease-associated donors. For an in-depth analysis, SP domain-specific Tcell lines are produced and analyzed for phenotype and function.…”

Section: Antigen-specific Cd4mentioning

confidence: 99%

“…Comprehensive in vitro and in vivo studies conducted on large (>50) sample pools of PBMCs, obtained from both cancer 45 and MTbinfected patients, 43,46 demonstrated significantly preferred proliferation across MHC, for the MUC1 TAA SP domain and 5 MTbderived SP domains, (including the known Ag 85 and 8 In select disorders (e.g., MUC1 TAA in cancer), the C-region, and, to some extent, the H-region SP fragments can reach the cell surface as independent molecules or as part of the entire antigen. This, in turn, can lead to the production of MUC1 SP-specific antibodies.…”

Section: Antigen-specific Cd4mentioning

confidence: 99%

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The use of signal peptide domains as vaccine candidates

Kovjazin¹,

Carmon²

2014

Human Vaccines & Immunotherapeutics

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Section: Antigen-specific Cd4mentioning

confidence: 97%

Section: Antigen-specific Cd4mentioning

confidence: 99%

Section: Antigen-specific Cd4mentioning

confidence: 99%

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The use of signal peptide domains as vaccine candidates

Kovjazin¹,

Carmon²

2014

Human Vaccines & Immunotherapeutics

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“…Generally, people focus on CD4 ϩ T cells and an adjuvant for Th1 cell stimulation in research for a TB vaccine. We primarily research peptides from stimulated ␥␦ T cells to analyze CDR3 sequences of ␥␦ T cells in people with TB (11)(12)(13)(14)(15). We attempted to apply this technology to TB-related antigen peptides.…”

Section: Discussionmentioning

confidence: 99%

“…Analyses of the characteristics of ␦2 CDR3 from ␥␦ T cells of TB patients may identify the predominant CDR3 and the sequence that specifically reacts with TB. Furthermore, ␣␤ T cells identify peptide or protein antigens that are related to M. tuberculosis (11)(12)(13)(14)(15), but little is known about the antigens recognized by ␥␦ T cells, except for various phosphoantigens. These phosphoantigens may not inhibit intracellular mycobacterial growth (16).…”

mentioning

confidence: 99%

Characteristics of the Vδ2 CDR3 Sequence of Peripheral γδ T Cells in Patients with Pulmonary Tuberculosis and Identification of a New Tuberculosis-Related Antigen Peptide

Ding

Wang

et al. 2015

Clin. Vaccine Immunol.

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c Antigen-specific ␥␦ T cells may play an important role in the immune response to Mycobacterium tuberculosis. However, little is known about the characteristics of the length distribution of the ␦2-chain complementarity determining region 3 (␦2 CDR3) of the ␥␦ T-cell receptor (TCR) in patients with active pulmonary tuberculosis (TB) on a large scale. In addition, M. tuberculosisactivated ␥␦ T cells potentially inhibit intracellular mycobacterial growth, but phosphoantigen-activated ␥␦ T cells do not. Only a few M. tuberculosis-related antigen peptides or proteins that are recognized by ␥␦ TCR have been identified. Twenty-four healthy donors (HDs) and 27 TB patients were included in the present study. The gene-scanning technique found that the ␦2 CDR3 length distribution patterns of ␥␦ TCR in TB patients were perturbed, and each pattern included different predominant CDR3 sequences. The predominant ␦2 CDR3 sequences of ␥␦ TCRs, which originated from TB patients and HD ␥␦ T cells that were stimulated by M. tuberculosis heat resistance antigen (Mtb-HAg), were used as probes to screen peptides recognized by ␥␦ TCR using a phage display library. We identified four peptides that bound to the predominant ␦2 CDR3 fragments and showed homology to M. tuberculosis genes in a BLAST search. Notably, one peptide was related to M. tuberculosis H37Rv (QHIPKPP), and this fragment was confirmed as a ligand for the ␥␦ TCR. Two fragments, Ag1 and Ag2, activated ␥␦ T cells from HD or TB patients. In summary, the ␦2 CDR3 lineage of TB patients apparently drifts, and the predominant ␦2 CDR3 sequence that recognizes M. tuberculosis may exhibit specificity. The identified M. tuberculosis-related antigen peptides may be used as vaccines or adjuvants for protective immunity against M. tuberculosis. Mycobacterium tuberculosis causes tuberculosis (TB), which is one of the most common serious chronic infectious diseases. TB is a threat to human health, especially with the increasing human immunodeficiency virus (HIV) pandemic and multidrugresistant strains of M. tuberculosis (1). An estimated 8.6 million people developed TB in 2012, and 1.3 million people died from the disease, including 320,000 deaths in people infected with HIV (2). Different pathways and cell types interact to mediate the innate and adaptive immunities against M. tuberculosis (3). The ␥␦ T-cell subset V␥9V␦2 cells was shown to play an important role in host immunity against M. tuberculosis in many studies (4-6). ␥␦ T cells generally recognize antigens in a non-major histocompatibility complex (MHC)-restricted manner, which is similar to how B cells directly recognize a ligand or antigen. The human ␦ chain is composed of eight V␦ gene fragments, two D␦ gene fragments, three J␦ gene fragments, and one C␦ gene fragment, and these fragments are located on the long arm of the 14th chromosome (7). Varying numbers of nucleotides (3 to 24) randomly insert into the connection area of the rearranged T-cell receptor (TCR) V␦ and form a VNDNJ sequence with a highly variable compleme...

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Peptide selection and antibody generation for the prospective immunorecognition of Cry1Ab16 protein of transgenic maize

et al. 2017

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The introduction of genes isolated from different Bacillus thuringiensis strains to express Cry-type toxins in transgenic crops is a common strategy to confer insect resistance traits. This work intended to extensively in silico analyse Cry1A(b)16 protein for the identification of peptide markers for the biorecognition of transgenic crops. By combining two different strategies based on several bioinformatic tools for linear epitope prediction, a set of seven peptides was successfully selected as potential Cry1A(b)16 immunogens. For the prediction of conformational epitopes, Cry1A(b)16 models were built on the basis of three independent templates of homologue proteins of Cry1A(a) and Cry1A(c) using an integrated approach. PcH_736-746 and PcH_876-886 peptides were selected as the best candidates, being synthesised and used for the production of polyclonal antibodies. To the best of our knowledge, this is the first attempt of selecting and defining linear peptides as immunogenic markers of Cry1A(b)-type toxins in transgenic maize.

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Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis

Cited by 10 publications

References 40 publications

The use of signal peptide domains as vaccine candidates

The use of signal peptide domains as vaccine candidates

Characteristics of the Vδ2 CDR3 Sequence of Peripheral γδ T Cells in Patients with Pulmonary Tuberculosis and Identification of a New Tuberculosis-Related Antigen Peptide

Peptide selection and antibody generation for the prospective immunorecognition of Cry1Ab16 protein of transgenic maize

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