scholarly journals Subunit Approach to Evaluation of the Immune Protective Potential of Leptospiral Antigens

2011 ◽  
Vol 18 (12) ◽  
pp. 2026-2030 ◽  
Author(s):  
Samuel R. Félix ◽  
Daiane D. Hartwig ◽  
Ana Paula C. Argondizzo ◽  
Éverton F. Silva ◽  
Fabiana K. Seixas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Proteins ◽  
Subunit Vaccine ◽  
Lethal Dose ◽  
Leptospira Interrogans ◽  
Significant Protection ◽  
Genome Sequences ◽  
Hamster Model ◽  
Content Type ◽  
The World

ABSTRACTLeptospirosis is the most widespread zoonosis in the world. Current vaccines are based on whole-cell preparations that cause severe side effects and do not induce satisfactory immunity. In light of the leptospiral genome sequences recently made available, several studies aimed at identification of protective recombinant immunogens have been performed; however, few such immunogens have been identified. The aim of this study was to evaluate 27 recombinant antigens to determine their potential to induce an immune response protective against leptospirosis in the hamster model. Experiments were conducted with groups of female hamsters immunized with individual antigen preparations. Hamsters were then challenged with a lethal dose ofLeptospira interrogans. Thirteen antigens induced protective immune responses; however, only recombinant proteins LIC10325 and LIC13059 induced significant protection against mortality. These results have important implications for the development of an efficacious recombinant subunit vaccine against leptospirosis.

scholarly journals Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

2012 ◽  
Vol 19 (5) ◽  
pp. 740-745 ◽  
Author(s):  
André A. Grassmann ◽  
Samuel R. Félix ◽  
Carolina Ximendes dos Santos ◽  
Marta G. Amaral ◽  
Amilton C. P. Seixas Neto ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
Subunit Vaccine ◽  
Lethal Dose ◽  
Control Group ◽  
Hamster Model ◽  
Content Type ◽  
B Subunit ◽  
Heat Labile ◽  
A Subunit

ABSTRACTLeptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species ofLeptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of theEscherichia coliheat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) ofLeptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P< 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.

scholarly journals Biochemical and Immunological Evaluation of Recombinant CS6-Derived Subunit EnterotoxigenicEscherichia coliVaccine Candidates

2019 ◽  
Vol 87 (3) ◽  
Author(s):  
Steven T. Poole ◽  
Milton Maciel ◽  
Premkumar Dinadayala ◽  
Kathleen E. Dori ◽  
Annette L. McVeigh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Proteins ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Strategy ◽  
Content Type ◽  
A Subunit ◽  
Folded Proteins ◽  
Immunological Evaluation

ABSTRACTCS6, a prevalent surface antigen expressed in nearly 20% of clinical enterotoxigenicEscherichia coli(ETEC) isolates, is comprised of two major subunit proteins, CssA and CssB. Using donor strand complementation, we constructed a panel of recombinant proteins of 1 to 3 subunits that contained combinations of CssA and/or CssB subunits and a donor strand, a C-terminal extension of 16 amino acids that was derived from the N terminus of either CssA or CssB. While the entire panel of recombinant proteins could be obtained as soluble, folded proteins, it was observed that the proteins possessing a heterologous donor strand, derived from the CS6 subunit different from the C-terminal subunit, had the highest degree of physical and thermal stability. Immunological characterization of the proteins, using a murine model, demonstrated that robust anti-CS6 immune responses were generated from fusions containing both CssA and CssB. Proteins containing only CssA were weakly immunogenic. Heterodimers, i.e., CssBA and CssAB, were sufficient to recapitulate the anti-CS6 immune response elicited by immunization with CS6, including the generation of functional neutralizing antibodies, as no further enhancement of the response was obtained with the addition of a third CS6 subunit. Our findings here demonstrate the feasibility of including a recombinant CS6 subunit protein in a subunit vaccine strategy against ETEC.

scholarly journals Serodiagnosis of Equine Leptospirosis by Enzyme-Linked Immunosorbent Assay Using Four Recombinant Protein Markers

2014 ◽  
Vol 21 (4) ◽  
pp. 478-483 ◽  
Author(s):  
Cuilian Ye ◽  
Weiwei Yan ◽  
Patrick L. McDonough ◽  
Sean P. McDonough ◽  
Hussni Mohamed ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Recombinant Proteins ◽  
Indirect Elisa ◽  
Zoonotic Diseases ◽  
Agglutination Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Leptospira Interrogans ◽  
Protein Markers ◽  
Content Type ◽  
The World

ABSTRACTLeptospirosis, caused byLeptospiraspp., is one of the most common zoonotic diseases in the world. We tested four recombinant proteins ofLeptospira interrogans, namely, rLipL21, rLoa22, rLipL32, and rLigACon4-8, to evaluate their potential for use as antigens for the diagnosis of equine leptospirosis. We employed equine sera (n= 130) that were microscopic agglutination test (MAT) negative and sera (n= 176) that were MAT positive for the 5 serovars that most commonly cause equine leptospirosis. The sensitivity and specificity of ELISA compared to MAT were 82.39% and 86.15%, respectively, for LigACon4-8, 77.84% and 92.31%, respectively, for Loa22, 77.84% and 86.15%, respectively, for LipL32, and 84.66% and 83.85%, respectively, for LipL21. When one of the two antigens was test positive, the sensitivity and specificity of ELISA were 93.75% and 78.46%, respectively, for rLigACon4-8 and LipL32, 93.18% and 76.15%, respectively, for rLigACon4-8 and LipL21, 89.77% and 80.77%, respectively, for rLigACon4-8 and Loa22, 91.48% and 78.46%, respectively, for LipL21 and Loa22, 93.75% and 76.92%, respectively, for LipL21 and LipL32, and 90.34% and 80.77%, respectively, for Loa22 and LipL32. In conclusion, we have developed an indirect ELISA utilizing rLigACon4-8, rLoa22, rLipL32, and rLipL21 as diagnostic antigens for equine leptospirosis. The use of four antigens in the ELISA was found to be sensitive and specific, the assay was easy to perform, and the results concurred with the results of the standardLeptospiraMAT.

scholarly journals Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Xiuran Wang ◽  
Amit K. Singh ◽  
Xiangmin Zhang ◽  
Wei Sun
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Rational Design ◽  
Lipid A ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Outer Membrane Vesicles ◽  
Vector System ◽  
Content Type ◽  
Monophosphoryl Lipid A

ABSTRACT A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in mice against subcutaneous challenge with 8 × 105 CFU (80,000 50% lethal dose [LD50]) and intranasal challenge with 5 × 103 CFU (50 LD50) of virulent Y. pestis. This protection was significantly superior to that resulting from vaccination with LcrV/alhydrogel or rF1-V/alhydrogel. At week 4 postimmunization, the OMV-immunized mice showed more robust titers of antibodies against LcrV, Y. pestis whole-cell lysate (YPL), and F1 antigen and more balanced IgG1:IgG2a/IgG2b-derived Th1 and Th2 responses than LcrV-immunized mice. Moreover, potent adaptive and innate immune responses were stimulated in the OMV-immunized mice. Our findings demonstrate that self-adjuvanting Y. pestis OMVs provide a novel plague vaccine candidate and that the rational design of OMVs could serve as a robust approach for vaccine development.

scholarly journals Changing Molecular Epidemiology of Vibrio cholerae Outbreaks in Shanghai, China

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Dalong Hu ◽  
Zhiqiu Yin ◽  
Chao Yuan ◽  
Pan Yang ◽  
Chengqian Qian ◽  
...  
Keyword(s):  
Southeast Asia ◽  
East Asia ◽  
Vibrio Cholerae ◽  
Watery Diarrhea ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
The World ◽  
Pandemic Strains

ABSTRACT The 7th cholera pandemic began in 1961 in Sulawesi, Indonesia, and then spread around the world in at least three waves. However, the lack of genome sequences for Vibrio cholerae strains under long-term surveillance in East Asia, especially in China, has restricted our understanding of the dynamics of the intracountry and intercountry evolution and transmission of the 7th-pandemic clones. In this study, we obtained the genome sequences of 60 V. cholerae strains isolated in Shanghai, the largest port in the world and the largest city in China, from 1961 to 2011. Our whole-genome-based phylogeny of 7th-pandemic strains revealed that all but one fell into five “stages,” most of which are single clades and share independent ancestors. Each stage dominated in succession for a period, with little overlap between them. In addition, two near-identical Shanghai strains belonging to a pre-7th-pandemic precursor and 4 nontoxigenic O1/O139 strains attributed to independent recombination events at the O-antigen loci were present. The major lineages of the 7th pandemic in Shanghai appeared to be closely related to V. cholerae strains isolated from South or Southeast Asia. Stage succession was consistently related to changes in society and human activity, implying that human-caused niche change may play a vital role in the cholera dynamics in Shanghai. IMPORTANCE V. cholerae is the causative agent of cholera, a life-threatening disease characterized by severe, watery diarrhea. The 7th pandemic started in Indonesia in 1961 and spread globally, currently infecting 1.3 million to 4 million people annually. Here, we applied whole-genome sequencing to analyze a long-term collection of V. cholerae clinical strains to reveal the phylogenetic background and evolutionary dynamics of the 7th pandemic in Shanghai, which had undergone breathtakingly rapid development in the last half-century. All but one of the Shanghai 7th-pandemic strains fell into five “stages” that were dominant in Shanghai and appeared to be closely related to 7th-pandemic strains of South or Southeast Asia. Our findings extended the understanding of the dynamics of the evolution and transmission of the 7th-pandemic clones in East Asia and the relationship between social changes and cholera epidemiology.

scholarly journals Oral Immunization with Escherichia coli Expressing a Lipidated Form of LigA Protects Hamsters against Challenge with Leptospira interrogans Serovar Copenhageni

2013 ◽  
Vol 82 (2) ◽  
pp. 893-902 ◽  
Author(s):  
Kristel Lourdault ◽  
Long-Chieh Wang ◽  
Ana Vieira ◽  
James Matsunaga ◽  
Rita Melo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Oral Vaccine ◽  
Oral Immunization ◽  
Reservoir Host ◽  
Leptospira Interrogans ◽  
Renal Tubules ◽  
Hamster Model ◽  
Content Type ◽  
E Coli ◽  
Humoral Immune

ABSTRACTLeptospirosis is a potentially fatal zoonosis transmitted by reservoir host animals that harbor leptospires in their renal tubules and shed the bacteria in their urine.Leptospira interrogansserovar Copenhageni transmitted fromRattus norvegicusto humans is the most prevalent cause of urban leptospirosis. We examinedL. interrogansLigA, domains 7 to 13 (LigA7-13), as an oral vaccine delivered byEscherichia colias a lipidated, membrane-associated protein. The efficacy of the vaccine was evaluated in a susceptible hamster model in terms of the humoral immune response and survival from leptospiral challenge. Four weeks of oral administration of liveE. coliexpressing LigA7-13 improved survival from intraperitoneal (i.p.) and intradermal (i.d.) challenge byL. interrogansserovar Copenhageni strain Fiocruz L1-130 in Golden Syrian hamsters. Immunization withE. coliexpressing LigA7-13 resulted in a systemic antibody response, and a significant LigA7-13 IgG level after the first 2 weeks of immunization was completely predictive of survival 28 days after challenge. As in previous LigA vaccine studies, all immunized hamsters that survived infection had renal leptospiral colonization and histopathological changes. In summary, an oral LigA-based vaccine improved survival from leptospiral challenge by either the i.p. or i.d. route.

scholarly journals Draft Genome Sequences of Four Different Strains Belonging to Leptospira interrogans Serovar Pomona Isolated from Mammals in the Island of Sardinia, Italy

2021 ◽  
Vol 10 (38) ◽  
Author(s):  
Ivana Piredda ◽  
Fabio Scarpa ◽  
Daria Sanna ◽  
Marco Casu ◽  
Maria Nicoletta Ponti ◽  
...  
Keyword(s):  
Wild Boar ◽  
Draft Genome ◽  
Zoonotic Disease ◽  
Leptospira Interrogans ◽  
Genome Sequences ◽  
Content Type ◽  
Leptospira Interrogans Serovar Pomona ◽  
Different Strains

Leptospirosis is a zoonotic disease of global importance caused by a pathogenic group of bacteria belonging to the genus Leptospira . Here, we report four draft genome sequences of Leptospira interrogans serovar Pomona isolated on Sardinia (Italy) from four different species of mammals (i.e., dolphin, wild boar, cow, and fox).

scholarly journals Draft Genome Sequences of Leptospira interrogans Serovar Copenhageni Strains Isolated from Patients with Weil’s Disease in Brazil

2020 ◽  
Vol 9 (7) ◽  
Author(s):  
Camilla N. R. Trindade ◽  
Pedro H. N. Panzenhagen ◽  
Ricardo M. Junqueira ◽  
Deyse C. V. Silva ◽  
Carlos A. Conte-Junior ◽  
...  
Keyword(s):  
Draft Genome ◽  
Leptospira Interrogans ◽  
Whole Genome ◽  
Pathogenic Species ◽  
Genome Sequences ◽  
Blood Samples ◽  
Content Type ◽  
Weil’S Disease ◽  
Weil's Disease ◽  
Severe Leptospirosis

Leptospirosis is a worldwide zoonosis caused by pathogenic species of Leptospira. In Brazil, this disease is endemic, presenting epidemic potential in rainy seasons. Here, we announce the whole-genome sequences of two L. interrogans serovar Copenhageni strains isolated from blood samples from two icteric patients associated with severe leptospirosis in Brazil.

scholarly journals Coagulases as Determinants of Protective Immune Responses against Staphylococcus aureus

2012 ◽  
Vol 80 (10) ◽  
pp. 3389-3398 ◽  
Author(s):  
Molly McAdow ◽  
Andrea C. DeDent ◽  
Carla Emolo ◽  
Alice G. Cheng ◽  
Barry N. Kreiswirth ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Von Willebrand Factor ◽  
Subunit Vaccine ◽  
Gene Sequences ◽  
Content Type ◽  
A Subunit ◽  
Von Willebrand ◽  
Willebrand Factor

ABSTRACTDuring infection,Staphylococcus aureussecretes two coagulases (Coa and von Willebrand factor binding protein [vWbp]), which, following an association with host prothrombin and fibrinogen, form fibrin clots and enable the establishment of staphylococcal disease. Within the genomes of differentS. aureusisolates, coagulase gene sequences are variable, and this has been exploited for a classification of types. We show here that antibodies directed against the variable prothrombin binding portion of coagulases confer type-specific immunity through the neutralization ofS. aureusclotting activity and protection from staphylococcal disease in mice. By combining variable portions of coagulases from North American isolates into hybrid Coa and vWbp proteins, a subunit vaccine that provided protection against challenge with different coagulase-typeS. aureusstrains in mice was derived.

scholarly journals Genome Sequences for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Strains Isolated from Different Water Sources

2021 ◽  
Vol 10 (24) ◽  
Author(s):  
Holly A. Gray ◽  
Patrick J. Biggs ◽  
Anne C. Midwinter ◽  
Sara A. Burgess
Keyword(s):  
Escherichia Coli ◽  
World Health ◽  
Beta Lactamase ◽  
Genome Sequences ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
The World ◽  
Mean Size ◽  
Health Organization

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are considered a critical priority by the World Health Organization. Presented here are two genome sequences of Escherichia coli strains isolated from New Zealand freshwater. The genome sequences’ mean size was 5.2 Mb, with a mean of 4,848 coding sequences. Both genomes carried the ESBL bla CTX-M gene.

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