The identification of novel immunogenic antigens as potential Shigella vaccine components

Abstract Background Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen. Methods Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections. Results Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody. Conclusions These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.

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Genome-Based Bioinformatic Selection of Chromosomal Bacillus anthracis Putative Vaccine Candidates Coupled with Proteomic Identification of Surface-Associated Antigens

Infection and Immunity ◽

10.1128/iai.71.8.4563-4579.2003 ◽

2003 ◽

Vol 71 (8) ◽

pp. 4563-4579 ◽

Cited By ~ 86

Author(s):

N. Ariel ◽

A. Zvi ◽

K. S. Makarova ◽

T. Chitlaru ◽

E. Elhanany ◽

...

Keyword(s):

Bacillus Anthracis ◽

Cellular Localization ◽

Sequence Similarity ◽

Selection Procedure ◽

Bioinformatic Analysis ◽

Genomic Research ◽

Vaccine Candidates ◽

Flight Mass Spectrometry ◽

Selection Of

ABSTRACT Bacillus anthracis (Ames strain) chromosome-derived open reading frames (ORFs), predicted to code for surface exposed or virulence related proteins, were selected as B. anthracis-specific vaccine candidates by a multistep computational screen of the entire draft chromosome sequence (February 2001 version, 460 contigs, The Institute for Genomic Research, Rockville, Md.). The selection procedure combined preliminary annotation (sequence similarity searches and domain assignments), prediction of cellular localization, taxonomical and functional screen and additional filtering criteria (size, number of paralogs). The reductive strategy, combined with manual curation, resulted in selection of 240 candidate ORFs encoding proteins with putative known function, as well as 280 proteins of unknown function. Proteomic analysis of two-dimensional gels of a B. anthracis membrane fraction, verified the expression of some gene products. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses allowed identification of 38 spots cross-reacting with sera from B. anthracis immunized animals. These spots were found to represent eight in vivo immunogens, comprising of EA1, Sap, and 6 proteins whose expression and immunogenicity was not reported before. Five of these 8 immunogens were preselected by the bioinformatic analysis (EA1, Sap, 2 novel SLH proteins and peroxiredoxin/AhpC), as vaccine candidates. This study demonstrates that a combination of the bioinformatic and proteomic strategies may be useful in promoting the development of next generation anthrax vaccine.

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Identification of a Candidate Streptococcus pneumoniae Core Genome and Regions of Diversity Correlated with Invasive Pneumococcal Disease

Infection and Immunity ◽

10.1128/iai.00316-06 ◽

2006 ◽

Vol 74 (8) ◽

pp. 4766-4777 ◽

Cited By ~ 119

Author(s):

Caroline Obert ◽

Jack Sublett ◽

Deepak Kaushal ◽

Ernesto Hinojosa ◽

Theresa Barton ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Core Genome ◽

Genomic Analysis ◽

Community Acquired Pneumonia ◽

Comparative Genomic ◽

Virulence Determinants ◽

Wild Type

ABSTRACT Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice.

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Abstract A014: Evaluation of the hollow fiber model as a highly predictive in vivo testing system for the selection of xenograft tumor models in cancer drug discovery

10.1158/1535-7163.targ-17-a014 ◽

2018 ◽

Cited By ~ 1

Author(s):

Annika Sinz ◽

Holger Weber ◽

Cynthia Obodozie

Keyword(s):

Drug Discovery ◽

Hollow Fiber ◽

Cancer Drug ◽

Testing System ◽

Xenograft Tumor ◽

Fiber Model ◽

Cancer Drug Discovery ◽

In Vivo Testing ◽

Selection Of

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Identification of Novel Vaccine Candidates againstCampylobacterthrough Reverse Vaccinology

Journal of Immunology Research ◽

10.1155/2016/5715790 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 28

Author(s):

Marine Meunier ◽

Muriel Guyard-Nicodème ◽

Edouard Hirchaud ◽

Alberto Parra ◽

Marianne Chemaly ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Reverse Vaccinology ◽

Poultry Meat ◽

Campylobacter Coli ◽

The European Union ◽

Vaccine Candidates ◽

Vaccine Antigens ◽

Potential Vaccine

Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union. Human cases are mainly due toCampylobacter jejuniorCampylobacter coli, and contamination is associated with the handling and/or consumption of poultry meat. In fact, poultry constitutes the bacteria’s main reservoir. A promising way of decreasing the incidence of campylobacteriosis in humans would be to decrease avian colonization. Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinalCampylobacterload in chickens. It is essential to identify and characterize new vaccine antigens. This study applied the reverse vaccinology approach to detect new vaccine candidates. The main criteria used to select immune proteins were localization, antigenicity, and number of B-epitopes. Fourteen proteins were identified as potential vaccine antigens.In vitroandin vivoexperiments now need to be performed to validate the immune and protective power of these newly identified antigens.

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Colonisation Capacity of Vibrio sp. strain Alg 3.1 and Abn 1.2 in the Gastrointestinal Tractof Gnotobiotic Abalone

Jurnal Penelitian Pendidikan IPA ◽

10.29303/jppipa.v6i2.339 ◽

2020 ◽

Vol 6 (2) ◽

pp. 173

Author(s):

Faturrahman Faturrahman ◽

Iman Rusmana ◽

Anja Meryandini

Keyword(s):

Observation Time ◽

Bacterial Isolates ◽

Wild Type ◽

In Vivo Testing ◽

Probiotic Strains ◽

Bacterial Treatment ◽

And Control ◽

Number Of Bacteria ◽

Selection Of

The use of Vibrio strains as probiotics in Indonesia is very rarely reported. The purpose of this study is to select and develop Vibrio probiotic strains that can increase the rate of abalone growth. The ability of bacterial isolates to colonize the abalone digestive tract is one of the important parameters in the selection of probiotic candidates. The research method consisted of 3 main stages namely modification of Vibrio sp isolates to rifampicin mutants, manufacture of gnotobiotic abalone and colonization capacity test. The treatment given in the colonization capacity test is a type of bacteria that consists of Vibrio sp. line Abn1.2RfR, Alg3.1RfR, combination of Abn1.2RfR + Alg3.1RfR, and control without the addition of Vibrio sp. Each type of bacterial treatment was entered in a 10 liter aquarium capacity containing 10 abalone size ± 3.5 cm. Feed in the form of Gracilaria cake containing Vibrio sp. (final concentration of 107 cfu / mL) was given at the beginning of the study. Abalone is observed for 24, 48 and 72 hours without water replacement. Then count the total number of bacteria and the number of agarolytic bacteria. The results showed that the growth characteristics of wild-type Vibrio with mutant Vibrio were not different.Thus it is expected that the use of the two mutant isolates for in vivo testing has the same effectiveness as the wild type.The capacity of colonization of a single isolate or a combination of rifampicin mutant Vibrio continues to decrease with increasing time of observation. Nevertheless, the percentage of mixed isolates remained higher than that of single isolates during the observation time

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In vitro teratogenicity testing using a 3D, embryo-like gastruloid system

10.1101/2021.03.30.437698 ◽

2021 ◽

Author(s):

Veronika Mantziou ◽

Peter Baillie-Benson ◽

Manuela Jaklin ◽

Stefan Kustermann ◽

Alfonso Martinez Arias ◽

...

Keyword(s):

Axial Patterning ◽

Fluorescent Reporters ◽

Lead Compounds ◽

Lineage Differentiation ◽

Aberrant Gene Expression ◽

Species Specific ◽

Aberrant Gene ◽

Selection Of

AbstractPharmaceuticals that are intended for use in patients of childbearing potential need to be tested for teratogenicity before marketing. Several pharmaceutical companies use animal-free in vitro models which allow a more rapid selection of lead compounds and contribute to 3Rs principles (‘replace, reduce and refine’) by streamlining the selection of promising compounds that are submitted to further regulatory studies in animals. Currently available in vitro models typically rely on adherent monolayer cultures or disorganized 3D structures, both of which lack the spatiotemporal and morphological context of the developing embryo. A newly developed 3D ‘gastruloid’ model has the potential to achieve a more reliable prediction of teratogenicity by providing a robust recapitulation of gastrulation-like events alongside morphological coordination at relatively high-throughput. In this first proof-of-concept study, we used both mouse and human gastruloids to examine a panel of seven reference compounds, with associated in vivo data and known teratogenic risk, to quantitatively assess in vitro teratogenicity. We observed several gross morphological effects, including significantly reduced elongation or decreased size of the gastruloids, upon exposure to several of the reference compounds. We also observed aberrant gene expression using fluorescent reporters, including SOX2, BRA, and SOX17, suggestive of multi-lineage differentiation defects and disrupted axial patterning. Finally, we saw that gastruloids recapitulated some of the known in vivo species-specific susceptibilities between their mouse and human counterparts. We therefore suggest that gastruloids represent a powerful tool for teratogenicity assessment by enabling relevant physiological recapitulation of early embryonic development, demonstrating their use as a novel in vitro teratogenic model system.

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Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets

Medical Microbiology and Immunology ◽

10.1007/s00430-019-00649-y ◽

2019 ◽

Vol 209 (3) ◽

pp. 243-263

Author(s):

Arno Thibau ◽

Alexander A. Dichter ◽

Diana J. Vaca ◽

Dirk Linke ◽

Adrian Goldman ◽

...

Keyword(s):

Vaccine Development ◽

Outer Membrane Proteins ◽

Host Cells ◽

Vaccine Candidates ◽

Bacterial Surface ◽

Major Interest ◽

Vaccine Antigens ◽

A Subunit ◽

Extracellular Environment ◽

Selection Of

AbstractThe current problem of increasing antibiotic resistance and the resurgence of numerous infections indicate the need for novel vaccination strategies more than ever. In vaccine development, the search for and the selection of adequate vaccine antigens is the first important step. In recent years, bacterial outer membrane proteins have become of major interest, as they are the main proteins interacting with the extracellular environment. Trimeric autotransporter adhesins (TAAs) are important virulence factors in many Gram-negative bacteria, are localised on the bacterial surface, and mediate the first adherence to host cells in the course of infection. One example is the Neisseria adhesin A (NadA), which is currently used as a subunit in a licensed vaccine against Neisseria meningitidis. Other TAAs that seem promising vaccine candidates are the Acinetobacter trimeric autotransporter (Ata), the Haemophilus influenzae adhesin (Hia), and TAAs of the genus Bartonella. Here, we review the suitability of various TAAs as vaccine candidates.

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