scholarly journals Reversion to virulence evaluation of a 9R vaccine strain of Salmonella enterica serovar gallinarum in commercial brown layers

2010 ◽  
Vol 12 (1) ◽  
pp. 47-52 ◽  
Author(s):  
AS Okamoto ◽  
A Menconi ◽  
GAM Gonçalves ◽  
TS Rocha ◽  
RF Andreatti Filho ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enterica

scholarly journals Improving Our Understanding of Salmonella enterica Serovar Paratyphi B through the Engineering and Testing of a Live Attenuated Vaccine Strain

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Ellen E. Higginson ◽  
Girish Ramachandran ◽  
Tracy H. Hazen ◽  
Dane A. Kania ◽  
David A. Rasko ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Enteric Fever ◽  
Sensu Stricto ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Heterologous Challenge ◽  
Paratyphi B ◽  
Homologous Challenge ◽  
Ideal Vaccine

ABSTRACT Enteric fever is caused by three Salmonella enterica serovars: Typhi, Paratyphi A, and Paratyphi B sensu stricto. Although vaccines against two of these serovars are licensed (Typhi) or in clinical development (Paratyphi A), as yet there are no candidates for S. Paratyphi B. To gain genomic insight into these serovars, we sequenced 38 enteric fever-associated strains from Chile and compared these with reference genomes. Each of the serovars was separated genomically based on the core genome. Genomic comparisons identified loci that were aberrant between serovars Paratyphi B sensu stricto and Paratyphi B Java, which is typically associated with gastroenteritis; however, the majority of these were annotated as hypothetical or phage related and thus were not ideal vaccine candidates. With the genomic information in hand, we engineered a live attenuated S. Paratyphi B sensu stricto vaccine strain, CVD 2005, which was capable of protecting mice from both homologous challenge and heterologous challenge with S. Paratyphi B Java. These findings extend our understanding of S. Paratyphi B and provide a viable vaccine option for inclusion in a trivalent live attenuated enteric fever vaccine formulation. IMPORTANCE We developed a live attenuated Salmonella enterica serovar Paratyphi B vaccine that conferred protection in mice against challenge with S. Paratyphi B sensu stricto and S. Paratyphi B Java, which are the causes of enteric fever and gastroenteritis, respectively. Currently, the incidence of invasive S. Paratyphi B sensu stricto infections is low; however, the development of new conjugate vaccines against other enteric fever serovars could lead to the emergence of S. Paratyphi B to fill the niche left by these other pathogens. As such, an effective S. Paratyphi B vaccine would be a useful tool in the armamentarium against Salmonella infections. Comparative genomics confirmed the serovar-specific groupings of these isolates and revealed that there are a limited number of genetic differences between the sensu stricto and Java strains, which are mostly hypothetical and phage-encoded proteins. The observed level of genomic similarity likely explains why we observe some cross-protection.

scholarly journals T- and B-Cell Immune Responses of Patients Who Had Undergone Colectomies to Oral Administration of Salmonella enterica Serovar Typhi Ty21a Vaccine

2003 ◽  
Vol 10 (3) ◽  
pp. 426-430 ◽  
Author(s):  
Jan Kilhamn ◽  
Samuel B. Lundin ◽  
Hans Brevinge ◽  
Ann-Mari Svennerholm ◽  
Marianne Jertborn
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
B Cell ◽  
Healthy Volunteers ◽  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Iga Antibody ◽  
Ifn Γ

ABSTRACT The capacity of an oral live attenuated Salmonella enterica serovar Typhi Ty21a vaccine to induce immune responses in patients who had undergone colectomies because of ulcerative colitis was evaluated, and these responses were compared with those of healthy volunteers. Purified CD4+ and CD8+ T cells from peripheral blood were stimulated in vitro by using the heat-killed Ty21a vaccine strain, and the proliferation and gamma interferon (IFN-γ) production were measured before and 7 or 8 days after vaccination. Salmonella-specific immunoglobulin A (IgA) and IgG antibody responses in serum along with IgA antibody responses in ileostomy fluids from the patients who had undergone colectomies were also evaluated. Three doses of vaccine given 2 days apart failed to induce proliferative T-cell responses in all the six patients who had undergone colectomies, and increases in IFN-γ production were found only among the CD8+ cells from three of the patients. In contrast, both proliferative responses and increased IFN-γ production were observed among CD4+ and CD8+ T cells from 3 and 6 of 10 healthy volunteers, respectively. Salmonella-specific IgA and/or IgG antibody responses in serum were observed for five (56%) of nine patients who had undergone colectomies and in 15 (88%) of 17 healthy volunteers. In ileostomy fluids, significant anti-Salmonella IgA antibody titer increases were detected in six (67%) of nine patients who had undergone colectomies. The impaired T- and B-cell immune responses found after vaccination in the circulation of patients who have undergone colectomies may be explained by a diminished colonization of the Ty21a vaccine strain due to the lack of a terminal ileum and colon.

scholarly journals Oral Immunization with a Salmonella enterica Serovar Typhi Vaccine Induces Specific Circulating Mucosa-Homing CD4+ and CD8+ T Cells in Humans

2002 ◽  
Vol 70 (10) ◽  
pp. 5622-5627 ◽  
Author(s):  
B. Samuel Lundin ◽  
Camilla Johansson ◽  
Ann-Mari Svennerholm
Keyword(s):  
T Cells ◽  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Magnetic Beads ◽  
Memory T Cells ◽  
Oral Immunization ◽  
Receptor Expression ◽  
Ifn Γ ◽  
Almost All

ABSTRACT The kinetics and homing characteristics of T-cell responses in humans after mucosal immunizations have not been well characterized. Therefore, we have investigated the magnitude and duration of such responses as well as the homing receptor expression of antigen-specific peripheral blood T cells by using an oral model vaccine, i.e., the live, attenuated Salmonella enterica serovar Typhi vaccine (Ty21a). Eight volunteers were each given three doses of the vaccine 2 days apart, and blood samples, from which CD4+ and CD8+ T cells were selected by the use of magnetic beads, were collected before vaccination and at regular intervals thereafter. To purify the potentially antigen-specific gut-homing T cells, CD45RA− integrin β7 + cells were further sorted by flow cytometry. The sorted cells were then stimulated in vitro with the serovar Typhi vaccine strain, and the proliferation of cells and the cytokine production were measured. Following vaccination, there was a large increase in both the proliferation of and the gamma interferon (IFN-γ) production by blood T cells stimulated with the vaccine strain. The responses were seen among both CD4+ and CD8+ T cells, although the CD8+ cells produced the largest amounts of IFN-γ. Peak responses were seen 7 to 14 days after the onset of vaccination. Furthermore, most of the IFN-γ produced by both CD4+ and CD8+ cells emanated from cells with the potential to home to mucosal tissues, as the integrin β7-expressing memory T cells produced around 10-fold more IFN-γ than the remaining populations. In conclusion, we demonstrate that oral vaccination with a live oral bacterial vaccine induces antigen-specific CD4+ and CD8+ memory T cells, almost all of which express the gut-homing integrin β7.

scholarly journals Construction, Genotypic and Phenotypic Characterization, and Immunogenicity of Attenuated ΔguaBA Salmonella enterica Serovar Typhi Strain CVD 915

2001 ◽  
Vol 69 (8) ◽  
pp. 4734-4741 ◽  
Author(s):  
Jin Yuang Wang ◽  
Marcela F. Pasetti ◽  
Fernando R. Noriega ◽  
Richard J. Anderson ◽  
Steven S. Wasserman ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Phase 1 ◽  
Lethal Dose ◽  
Phenotypic Characterization ◽  
Typhoid Vaccine ◽  
Wild Type ◽  
Gene Encoding

ABSTRACT A promising live attenuated typhoid vaccine candidate strain for mucosal immunization was developed by introducing a deletion in theguaBA locus of pathogenic Salmonella entericaserovar Typhi strain Ty2. The resultant ΔguaBA mutant, serovar Typhi CVD 915, has a gene encoding resistance to arsenite replacing the deleted sequence within guaBA, thereby providing a marker to readily identify the vaccine strain. CVD 915 was compared in in vitro and in vivo assays with wild-type strain Ty2, licensed live oral typhoid vaccine strain Ty21a, or attenuated serovar Typhi vaccine strain CVD 908-htrA (harboring mutations inaroC, aroD, and htrA). CVD 915 was less invasive than CVD 908-htrA in tissue culture and was more crippled in its ability to proliferate after invasion. In mice inoculated intraperitoneally with serovar Typhi and hog gastric mucin (to estimate the relative degree of attenuation), the 50% lethal dose of CVD 915 (7.7 × 107 CFU) was significantly higher than that of wild-type Ty2 (1.4 × 102 CFU) and was only slightly lower than that of Ty21a (1.9 × 108CFU). Strong serum O and H antibody responses were recorded in mice inoculated intranasally with CVD 915, which were higher than those elicited by Ty21a and similar to those stimulated by CVD 908-htrA. CVD 915 also elicited potent proliferative responses in splenocytes from immunized mice stimulated with serovar Typhi antigens. Used as a live vector, CVD 915(pTETlpp) elicited high titers of serum immunoglobulin G anti-fragment C. These encouraging preclinical data pave the way for phase 1 clinical trials with CVD 915.

scholarly journals Genome Sequence of Salmonella enterica Serovar Typhi Oral Vaccine Strain Ty21a

2013 ◽  
Vol 1 (4) ◽  
Author(s):  
D. Xu ◽  
J. O. Cisar ◽  
F. Poly ◽  
J. Yang ◽  
J. Albanese ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Genome Sequence ◽  
Salmonella Enterica ◽  
Oral Vaccine ◽  
Salmonella Enterica Serovar Typhi

scholarly journals Immune Responses to Recombinant Pneumococcal PspA Antigen Delivered by Live Attenuated Salmonella enterica Serovar Typhimurium Vaccine

2002 ◽  
Vol 70 (4) ◽  
pp. 1739-1749 ◽  
Author(s):  
Ho Young Kang ◽  
Jay Srinivasan ◽  
Roy Curtiss
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Outer Membrane Proteins ◽  
Oral Immunization ◽  
Recombinant Antigen ◽  
Heterologous Antigen ◽  
Recombinant Antigens ◽  
Serovar Typhimurium ◽  
Type Response

ABSTRACT Attenuated Salmonella enterica serovar Typhimurium expressing recombinant antigens from other pathogens elicits primarily a Th1-type dominant immune response to both recombinant and Salmonella antigens. The immunogenicity and appropriate subcellular location of the recombinant antigen in the Salmonella vaccine strain may contribute to augmenting immune responses by facilitating adequate exposure of recombinant antigen to antigen-presenting cells for processing. To allow for secretion from gram-negative bacteria and overexpression of antigen, a DNA fragment encoding a highly antigenic α-helical region of PspA (pneumococcal surface protein A) was subcloned downstream from the β-lactamase signal sequence in the multicopy Asd+ pYA3493 vector to create pYA3494. pYA3493 was derived from a class of Asd+ vectors with reduced expression of Asd to minimize selective disadvantage and enhance immunization of expressed recombinant antigens. The S. enterica serovar Typhimurium vaccine strain was constructed by the introduction of deletion mutations Δcrp-28 and ΔasdA16. Approximately 50% of the recombinant PspA (rPspA) expressed in a Salmonella strain harboring pYA3494 was detected in the combined supernatant and periplasmic fractions of broth-grown recombinant Salmonella. After a single oral immunization in BALB/c mice with 109 CFU of the recombinant Salmonella vaccine strain carrying pYA3494, immunoglobulin G (IgG) antibody responses were stimulated to both the heterologous antigen rPspA and Salmonella lipopolysaccharide (LPS) and outer membrane proteins (OMPs). About half, and even more at later times after immunization, of the antibodies induced to rPspA were IgG1 (indicating a Th2-type response), whereas 60 to 70% of the antibodies to LPS and 80 to 90% of those to OMPs were IgG2a (indicating a Th1-type response). A sublethal infection with Streptococcus pneumoniae WU2 boosted PspA antibody levels and maintained IgG2a/IgG1 ratios similar to those seen before the challenge. Oral immunization with Salmonella-PspA vaccine protected 60% of immunized mice from death after intraperitoneal challenge with 50 times the 50% lethal dose of virulent S. pneumoniae WU2.

scholarly journals Factorial Design to Prepare, Select and Determine a Vaccine Strain of Salmonella enterica Serotype Enteritidis 82139

2021 ◽  
Vol 17 (4) ◽  
pp. 125-136
Author(s):  
Liliana Veronica Villanueva-Alva ◽  
Rafael Rotger-Anglada ◽  
Raul Antonio Beltran–Orbegoso
Keyword(s):  
Factorial Design ◽  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serotype Enteritidis

scholarly journals Construction of a tetR-Integrated Salmonella enterica Serovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein of Plasmodium falciparum for Applications in Human Vaccine Production

2002 ◽  
Vol 70 (4) ◽  
pp. 2029-2038 ◽  
Author(s):  
Feng Qian ◽  
Weiqing Pan
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Expression Vector ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Inducible Expression ◽  
Luciferase Reporter ◽  
Foreign Gene

ABSTRACT Attenuated Salmonella strains are an attractive live vector for delivery of a foreign antigen to the human immune system. However, the problem with this vector lies with plasmid segregation and the low level of expression of the foreign gene in vivo when constitutive expression is employed, leading to a diminished immune response. We have established inducible expressions of foreign genes in the Salmonella enterica serovar Typhi CVD908 vaccine strain using the tetracycline response regulatory promoter. To set up this system, a tetracycline repressor (tetR) was integrated into a defined ΔaroC locus of the chromosome via suicide plasmid pJG12/tetR-neo. To remove the neo gene conferring kanamycin resistance from the locus, a cre expression vector under the control of the tetracycline response promoter was transformed into the clone; expression of the Cre recombinase excised the neo gene and generated the end strain CVD908-tetR. Expression of the luciferase reporter gene in this strain is dependent on the presence of tetracycline in the medium and can be regulated up to 4,773-fold. Moreover, the tightly controlled expression of major merozoite surface protein 1 (MSP1) and parts of Plasmodium falciparum was achieved, and the product yield was increased when the inducible expression system was employed. Inoculation of bacteria harboring plasmid pZE11/MSP142 in mice produced the protein in liver and spleen controlled by the inducer. The persistence of the plasmid-carrying bacteria in mice was determined. Peak colonization of both liver and spleen was detected on the third day postinoculation and was followed by a decline in growth curves. After 14 days postinfection, the majority of the bacteria (>90%) recovered from the liver and spleen of the mice retained the plasmid when expression was induced; this clearly indicated that stability of the expression vector in vivo was improved by inducible expression. Establishment of the regulatory system in the vaccine strain may broaden the range of its use by enhancing plasmid stability and expression levels in vivo. Moreover, the availability of the vaccine strain inducibly expressing the entire MSP1 provides possibilities for examining its immunogenicity, particularly the cellular response in animal models.

scholarly journals Salmonella enterica Serovar Typhimurium trxA Mutants Are Protective against Virulent Challenge and Induce Less Inflammation than the Live-Attenuated Vaccine Strain SL3261

2009 ◽  
Vol 78 (1) ◽  
pp. 326-336 ◽  
Author(s):  
S. E. Peters ◽  
G. K. Paterson ◽  
E. S. D. Bandularatne ◽  
H. C. Northen ◽  
S. Pleasance ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Salmonella Enterica ◽  
Parent Strain ◽  
Reductase Activity ◽  
Gene Cassette ◽  
Kanamycin Resistance ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Oxidative Stresses ◽  
Serovar Typhimurium

ABSTRACT In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4+ and CD8+ T cells and B lymphocytes in the spleen and reduced infiltration by CD11b+ cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

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