scholarly journals Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals.

1987 ◽  
Vol 166 (5) ◽  
pp. 1510-1524 ◽  
Author(s):  
S C Szu ◽  
A L Stone ◽  
J D Robbins ◽  
R Schneerson ◽  
J B Robbins
Keyword(s):  
Typhoid Fever ◽  
Rhesus Monkeys ◽  
Capsular Polysaccharide ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Protective Action ◽  
The United States ◽  
Laboratory Animals ◽  
Protein Conjugates ◽  
High Yields

The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions.

scholarly journals Antigenicity and Immunogenicity of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b

2004 ◽  
Vol 72 (12) ◽  
pp. 7115-7123 ◽  
Author(s):  
V. Fernández-Santana ◽  
Félix Cardoso ◽  
Arlene Rodriguez ◽  
Tania Carmenate ◽  
Luis Peña ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Capsular Polysaccharide ◽  
Cost Effective ◽  
Laboratory Animals ◽  
Haemophilus Influenzae Type ◽  
Response Patterns ◽  
Industrialized Countries ◽  
Type B ◽  
Protein Conjugates ◽  
Synthetic Antigens

ABSTRACT Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.

scholarly journals Mimotopes of the Vi Antigen of Salmonella enterica Serovar Typhi Identified from Phage Display Peptide Library

2003 ◽  
Vol 10 (6) ◽  
pp. 1078-1084 ◽  
Author(s):  
Swee-Seong Tang ◽  
Wen-Siang Tan ◽  
Shamala Devi ◽  
Lin-Fa Wang ◽  
Tikki Pang ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Salmonella Enterica ◽  
Capsular Polysaccharide ◽  
Protective Antigen ◽  
Peptide Library ◽  
Peptide Sequence ◽  
Phage Display Peptide Library ◽  
Phage Displayed Peptide Library ◽  
Immunodominant Epitopes ◽  
Vi Antigen

ABSTRACT The capsular polysaccharide Vi antigen (ViCPS) is an essential virulence factor and also a protective antigen of Salmonella enterica serovar Typhi. A random 12-mer phage-displayed peptide library was used to identify mimotopes (epitope analogues) of this antigen by panning against a ViCPS-specific monoclonal antibody (MAb) ATVi. Approximately 75% of the phage clones selected in the fourth round carried the peptide sequence TSHHDSHGLHRV, and the rest of the clones harbored ENHSPVNIAHKL and other related sequences. These two sequences were also obtained in a similar panning process by using pooled sera from patients with a confirmed diagnosis of typhoid fever, suggesting they mimic immunodominant epitopes of ViCPS antigens. Binding of MAb ATVi to the mimotopes was specifically blocked by ViCPS, indicating that they interact with the same binding site (paratope) of the MAb. Data and reagents generated in this study have important implications for the development of peptide-base diagnostic tests and peptide vaccines and may also provide a better understanding of the pathogenesis of typhoid fever.

scholarly journals Characterization of Citrobacter sp. line 328 as a source of Vi for a Vi-CRM197 glycoconjugate vaccine against Salmonella Typhi

2012 ◽  
Vol 6 (11) ◽  
pp. 763-773 ◽  
Author(s):  
Simona Rondini ◽  
Francesca Micoli ◽  
Luisa Lanzilao ◽  
Ivan Pisoni ◽  
Vito Di Cioccio ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Capsular Polysaccharide ◽  
Salmonella Typhi ◽  
Defined Medium ◽  
Industrial Scale ◽  
Scale Production ◽  
Populations At Risk ◽  
Vi Capsular Polysaccharide ◽  
High Yields ◽  
Antibody Levels

Introduction: Salmonella enterica serovar Typhi is the causative agent of typhoid fever with over 22 million cases and over 200,000 deaths reported annually. A vaccine is much needed for use in young children and the Novartis Vaccines Institute for Global Health (NVGH) is developing a conjugate vaccine which targets S. Typhi Vi capsular polysaccharide. Methodology: Here we describe a method suitable for industrial scale production of the Vi antigen based on expression by a Citrobacter line. We optimized the production of Vi by selecting a suitable Citrobacter strain (Citrobacter 328) that yields high and stable expression of Vi in chemically defined medium under industrial-scale fermentation conditions. Results: Vi-CRM197 made using Vi from Citrobacter 328 elicited high anti-Vi antibody levels in mice and rabbits. Conclusions: Citrobacter 328 is a suitable strain for production of Vi for conjugate anti-Typhi vaccines. Being a BSL-1 organism, which grows in defined medium and stably produces high yields of Vi, it offers excellent potential for safe production of inexpensive vaccines for populations at risk of typhoid fever.

Animal Pain Scales in Public Policy

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 41-50
Author(s):  
F. Barbara Orlans
Keyword(s):  
Public Policy ◽  
Animal Welfare ◽  
The United States ◽  
Pain Scale ◽  
Laboratory Animals ◽  
Practical Applications ◽  
Animal Pain ◽  
Pain Scales ◽  
History Of ◽  
And Control

Pain scales classify the severity of pain inflicted on laboratory animals from little or none up to severe. A pain scale as part of public policy serves beneficial purposes that promote animal welfare. It can be used to educate people about the two alternatives of refinement and replacement, and the need to reduce animal pain. Furthermore, a pain scale has practical applications: 1) in review procedures for animal welfare concerns; 2) in developing policies on the use of animals in education; and 3) as a basis for collecting national data on animal experimentation, so that meaningful data can be collected on trends in reduction and control in animal pain. So far, only a few countries (including Sweden, the Netherlands, Canada and New Zealand) have adopted pain scales as part of their public policy. Most countries, including the United States, have not yet done so. The history of the development and adoption of pain scales by various countries is described and the case is presented for wider adoption of a pain scale in countries not currently using one.

scholarly journals Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orhan Sahin ◽  
Samantha A. Terhorst ◽  
Eric R. Burrough ◽  
Zhangqi Shen ◽  
Zuowei Wu ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Campylobacter Jejuni ◽  
Capsular Polysaccharide ◽  
Systemic Infection ◽  
The United States ◽  
Content Type ◽  
Model Following ◽  
Capsule Production ◽  
Guinea Pig Model

ABSTRACT Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.

scholarly journals A Recombinant Carboxy-Terminal Domain of the Protective Antigen of Bacillus anthracis Protects Mice against Anthrax Infection

2002 ◽  
Vol 70 (3) ◽  
pp. 1653-1656 ◽  
Author(s):  
Helen C. Flick-Smith ◽  
Nicola J. Walker ◽  
Paula Gibson ◽  
Helen Bullifent ◽  
Sarah Hayward ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Fusion Proteins ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Anthrax Infection ◽  
Carboxy Terminal ◽  
Domain 4

ABSTRACT The immunogenicity and protective efficacy of overlapping regions of the protective antigen (PA) polypeptide, cloned and expressed as glutathione S-transferase fusion proteins, have been assessed. Results show that protection can be attributed to individual domains and imply that it is domain 4 which contains the dominant protective epitopes of PA.

scholarly journals Kinetics of Targeted Phage Rescue in a Mouse Model of SystemicEscherichia coliK1

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
György Schneider ◽  
Nikolett Szentes ◽  
Marianna Horváth ◽  
Ágnes Dorn ◽  
Alysia Cox ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Protective Efficacy ◽  
Lytic Bacteriophage ◽  
E Coli ◽  
Causative Agents ◽  
High Level ◽  
Systemic Infections ◽  
Kinetics Of

Escherichia (E.) coliK1 strains remain common causative agents of neonatal sepsis and meningitis. We have isolated a lytic bacteriophage (ΦIK1) againstE. colistrain IHE3034 and tested its specificityin vitro, as well as distribution and protective efficacyin vivo. The phage was shown to be specific to the K1 capsular polysaccharide. In the lethal murine model, a high level of protection was afforded by the phage with strict kinetics. A single dose of 1 x 108phage particles administered 10 and 60 minutes following the bacterial challenge elicited 100 % and 95 % survival, respectively. No mice could be rescued if phage administration occurred 3 hours postinfection. Tissue distribution surveys in the surviving mice revealed that the spleen was the primary organ in which accumulation of active ΦIK1 phages could be detected two weeks after phage administration. These results suggest that bacteriophages have potential as therapeutic agents in the control of systemic infections.

scholarly journals Identification of a Protein Subset of the Anthrax Spore Immunome in Humans Immunized with the Anthrax Vaccine Adsorbed Preparation

2005 ◽  
Vol 73 (9) ◽  
pp. 5685-5696 ◽  
Author(s):  
Indira T. Kudva ◽  
Robert W. Griffin ◽  
Jeonifer M. Garren ◽  
Stephen B. Calderwood ◽  
Manohar John
Keyword(s):  
Drug Targets ◽  
Protective Antigen ◽  
Hypothetical Protein ◽  
The United States ◽  
Surface Proteins ◽  
Spore Surface ◽  
Expression Library ◽  
Anthrax Vaccine ◽  
Anthrax Spore ◽  
Anthrax Vaccines

ABSTRACTWe identified spore targets of Anthrax Vaccine Adsorbed (AVA)-induced immunity in humans by screening recombinant clones of a previously generated, limited genomicBacillus anthracisSterne (pXO1+, pXO2−) expression library of putative spore surface (spore-associated [SA]) proteins with pooled sera from human adults immunized with AVA (immune sera), the anthrax vaccine currently approved for use by humans in the United States. We identified 69 clones that reacted specifically with pooled immune sera but not with pooled sera obtained from the same individuals prior to immunization. Positive clones expressed proteins previously identified as localized on the anthrax spore surface, proteins highly expressed during spore germination, orthologs of proteins of diverse pathogens under investigation as drug targets, and orthologs of proteins contributing to the virulence of both gram-positive and gram-negative pathogens. Among the reactive clones identified by this immunological screen was one expressing a 15.2-kDa hypothetical protein encoded by a gene with no significant homology to sequences contained in databases. Further studies are required to define the subset of SA proteins identified in this study that contribute to the virulence of this pathogen. We hypothesize that optimal delivery of a subset of SA proteins identified by such studies to the immune system in combination with protective antigen (PA), the principal immunogen in AVA, might facilitate the development of defined, nonreactogenic, more-efficacious PA-based anthrax vaccines. Future studies might also facilitate the identification of SA proteins with potential to serve as targets for drug design, spore inactivation, or spore detection strategies.

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