Immunome-derived vaccines

Groot, Anne S. De

doi:10.1517/14712598.4.6.767

Cited by 25 publications

(12 citation statements)

References 25 publications

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“…Amoung these is cathepsin L, which induces significant reduction in both worm burden and egg output. Vaccinating with the epitope only, rather than with the entire organism or the isolated antigen, could be much safer, and may be as effective (De Groot, 2004). Random peptide phage libraries have been successfully used for the identification of immunogenic epitopes or mimotopes, and induce humoral immune responses in animals (Smith & Pretenko, 1997).…”

Section: Discussionmentioning

confidence: 99%

Proteolytic activity inFasciola hepaticais reduced by the administration of cathepsin L mimotopes

Villa-Mancera

Quiróz-Romero²,

Correa

et al. 2010

J. Helminthol.

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The objective of this study was to assess the proteolytic activity of Fasciola hepatica cathepsins in liver sections from mice vaccinated with phage clones of cathepsin L mimotopes, using the film in situ zymography technique. Female BALB/c mice were immunized three times with 2.5 x 10¹¹ phage particles without adjuvant. Animals vaccinated with phage clones produced high titres of anti-mimotope antibodies and a significant reduction in fluke burden was observed following challenge with metacercariae of F. hepatica. The proteolytic activity in hepatic tissue was reduced after the immunization with phage clones.

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Section: Discussionmentioning

confidence: 99%

Proteolytic activity inFasciola hepaticais reduced by the administration of cathepsin L mimotopes

Villa-Mancera

Quiróz-Romero²,

Correa

et al. 2010

J. Helminthol.

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“…Most recently, Han and colleagues (22) reported an elegant TCR profiling and phenotyping approach using the MiSeq platform. In parallel, many immunomics tools have evolved, including immunoinformatics enabling in silico prediction of epitopes for whole proteomes following in vitro validation of peptide candidates by HLA binding and cellular immune assays (23,24). In summary, these methods focus on either the identification of T-cell epitopes or the analysis of TCR repertoires, but none of them combines both, matching epitopes with TCR repertoire.…”

Section: Introductionmentioning

confidence: 99%

Functional TCR Retrieval from Single Antigen-Specific Human T Cells Reveals Multiple Novel Epitopes

Simon

Omokoko

Breitkreuz

et al. 2014

Cancer Immunology Research

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The determination of the epitope specificity of disease-associated T-cell responses is relevant for the development of biomarkers and targeted immunotherapies against cancer, autoimmune, and infectious diseases. The lack of known T-cell epitopes and corresponding T-cell receptors (TCR) for novel antigens hinders the efficient development and monitoring of new therapies. We developed an integrated approach for the systematic retrieval and functional characterization of TCRs from single antigen-reactive T cells that includes the identification of epitope specificity. This is accomplished through the rapid cloning of full-length TCR-a and TCR-b chains directly from single antigen-specific CD8 þ or CD4 þ T lymphocytes. The functional validation of cloned TCRs is conducted using in vitro-transcribed RNA transfer for expression of TCRs in T cells and HLA molecules in antigen-presenting cells. This method avoids the work and bias associated with repetitive cycles of in vitro T-cell stimulation, and enables fast characterization of antigen-specific T-cell responses. We applied this strategy to viral and tumor-associated antigens (TAA), resulting in the retrieval of 56 unique functional antigenspecific TCRs from human CD8 þ and CD4 þ T cells (13 specific for CMV-pp65, 16 specific for the well-known TAA NY-ESO-1, and 27 for the novel TAA TPTE), which are directed against 39 different epitopes. The proof-of-concept studies with TAAs NY-ESO-1 and TPTE revealed multiple novel TCR specificities. Our approach enables the rational development of immunotherapy strategies by providing antigen-specific TCRs and immunogenic epitopes.

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“…Antigen discovery by targeted computational screening of the complete repertoire of proteins potentially encoded by a pathogen is an approach termed "reverse vaccinology" (1,27). The specific classes of proteins selected by in silico analysis include mostly surface-exposed and/or exported proteins with putative involvement in virulence.…”

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confidence: 99%

Search for Bacillus anthracis Potential Vaccine Candidates by a Functional Genomic-Serologic Screen

Gat¹,

Grosfeld²,

Ariel³

et al. 2006

Infect Immun

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Bacillus anthracis proteins that possess antigenic properties and are able to evoke an immune response were identified by a reductive genomic-serologic screen of a set of in silico-preselected open reading frames (ORFs). The screen included in vitro expression of the selected ORFs by coupled transcription and translation of linear PCR-generated DNA fragments, followed by immunoprecipitation with antisera from B. anthracis-infected animals. Of the 197 selected ORFs, 161 were chromosomal and 36 were on plasmids pXO1 and pXO2, and 138 of the 197 ORFs had putative functional annotations (known ORFs) and 59 had no assigned functions (unknown ORFs). A total of 129 of the known ORFs (93%) could be expressed, whereas only 38 (64%) of the unknown ORFs were successfully expressed. All 167 expressed polypeptides were subjected to immunoprecipitation with the anti-B. anthracis antisera, which revealed 52 seroreactive immunogens, only 1 of which was encoded by an unknown ORF. The high percentage of seroreactive ORFs among the functionally annotated ORFs (37%; 51/129) attests to the predictive value of the bioinformatic strategy used for vaccine candidate selection. Furthermore, the experimental findings suggest that surface-anchored proteins and adhesins or transporters, such as cell wall hydrolases, proteins involved in iron acquisition, and amino acid and oligopeptide transporters, have great potential to be immunogenic. Most of the seroreactive ORFs that were tested as DNA vaccines indeed appeared to induce a humoral response in mice. We list more than 30 novel B. anthracis immunoreactive virulence-related proteins which could be useful in diagnosis, pathogenesis studies, and future anthrax vaccine development.

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Immunome-derived vaccines

Cited by 25 publications

References 25 publications

Proteolytic activity inFasciola hepaticais reduced by the administration of cathepsin L mimotopes

Proteolytic activity inFasciola hepaticais reduced by the administration of cathepsin L mimotopes

Functional TCR Retrieval from Single Antigen-Specific Human T Cells Reveals Multiple Novel Epitopes

Search for Bacillus anthracis Potential Vaccine Candidates by a Functional Genomic-Serologic Screen

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