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.

scholarly journals Safety and Immunogenicity of Vi Conjugate Vaccines for Typhoid Fever in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam

1999 ◽  
Vol 67 (11) ◽  
pp. 5806-5810 ◽  
Author(s):  
Zuzana Kossaczka ◽  
Feng-Ying C. Lin ◽  
Vô Anh Ho ◽  
Nguyen Thi Thanh Thuy ◽  
Phan Van Bay ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Typhoid Fever ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Salmonella Typhi ◽  
Enzyme Linked Immunosorbent Assay ◽  
Conjugate Vaccines ◽  
Local Reactions ◽  
Antibody Levels ◽  
Igg Level

ABSTRACT The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using eitherN-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA1) or adipic acid dihydrazide (ADH; Vi-rEPA2) as linkers. None of the recipients experienced a temperature of >38.5°C or significant local reactions. One injection of Vi-rEPA2 into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA2, Vi-rEPA1, and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA1 and Vi with respect to Vi-rEPA2). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA2, Vi-rEPA1, and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA1 and Vi with respect to Vi-rEPA2); all were higher than the preinjection levels (P = 0.0001). Vi-rEPA2 also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA2 elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA1(P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA2 and from 28.9 to 83.0 EU for Vi-rEPA1. At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA2 and 12.8 versus 0.33 for Vi-rEPA1; P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA2 in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA2conjugate warrant further investigation.

scholarly journals Chromatographically purified Vi-capsular polysaccharide antigen for vaccination against Typhoid fever

1998 ◽  
pp. 240
Author(s):  
I.V. Ankudinov ◽  
M.E. Golovina ◽  
V.L. L'vov ◽  
N.P. Vaneeva ◽  
I.C. Verner ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Capsular Polysaccharide ◽  
Polysaccharide Antigen ◽  
Vi Capsular Polysaccharide

Clinical and serological responses following primary and booster immunization with Salmonella typhi Vi capsular polysaccharide vaccines

Vaccine ◽  
1994 ◽  
Vol 12 (3) ◽  
pp. 195-199 ◽  
Author(s):  
Wendy A. Keitel ◽  
Nanette L. Bond ◽  
John M. Zahradnik ◽  
Tod A. Cramton ◽  
John B. Robbins
Keyword(s):  
Capsular Polysaccharide ◽  
Salmonella Typhi ◽  
Booster Immunization ◽  
Vi Capsular Polysaccharide

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.

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers

Vaccine ◽  
2015 ◽  
Vol 33 (33) ◽  
pp. 4141-4145 ◽  
Author(s):  
Louise Roggelin ◽  
Christof D. Vinnemeier ◽  
Johanna Fischer-Herr ◽  
Brandi T. Johnson-Weaver ◽  
Thierry Rolling ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Healthy Adult ◽  
Salmonella Typhi ◽  
Serological Response ◽  
Vi Capsular Polysaccharide
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