pectins and Typhoid-Fever

Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial.. Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18-45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed.. No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4-fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R(2)=0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults.. The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. ClinicalTrial.gov identifier: NCT00277147, NIH Protocol ID number: OH06-CH-0070, FDA BB Investigation New Drug (IND) number 6989.

Topics: Acetylation; Adolescent; Adult; Antibodies, Bacterial; Citrus; Female; Humans; Immunoglobulin G; Male; Pectins; Polysaccharides, Bacterial; Recombinant Proteins; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Conjugate; Young Adult

Topics: Acetylation; Animals; Antibodies, Bacterial; Antibody Formation; Disease Models, Animal; Immunization, Secondary; Immunogenicity, Vaccine; Immunoglobulin G; Immunologic Memory; Mice; Pectins; Polysaccharides, Bacterial; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Synthetic

Pectin, a plant polysaccharide, is mostly a linear homopolymer of poly(1-->4)-alpha-D-GalpA with < 5% neutral sugars: its molecular size has a broad distribution around 400 kDa, and the degree of esterification is < 5%. The structure of the capsular polysaccharide of Salmonella typhi (Vi) differs from pectin in that it is N acetylated at C-2 and O acetylated at C-3, and has a molecular size of approximately 2 x 10(3) kDa. There is no serological cross-reaction between pectin and Vi. Pectin, when O acetylated at C-2 and C-3, is antigenically identical to Vi in double immunodiffusion. Unlike Vi, O-acetylated pectin (OAcPec) is not immunogenic in mice, probably because of its comparatively low molecular weight. After storage at 3 to 8 degrees C for 3 months, there was no change in the O-acetyl content or the M(r) of OAcPec. At 60 degrees C, the M(r) of OAcPec declined more rapidly than that of Vi. OAcPec conjugated to tetanus toxoid elicited Vi antibodies in mice, and reinjection elicited a booster response. The levels of Vi antibodies elicited by OAcPec-tetanus toxoid conjugates were lower than those elicited by Vi conjugates, but these differences were not statistically significant. OAcPec has some advantages because it can be measured by standardized colorimetric assays and because it forms more soluble conjugates with proteins than does Vi. One disadvantage is that its glycosidic bond is not as stable as that of Vi. The use of a plant polysaccharide, pectin, as an immunogen for prevention of a systemic infection caused by a capsulated pathogen (S. typhi) provides a novel approach to improve the preparation and immunogenicity of polysaccharide-based vaccines.

Topics: Adjuvants, Immunologic; ADP Ribose Transferases; Animals; Antibodies, Bacterial; Antibody Formation; Antigens, Bacterial; Bacterial Toxins; Carbohydrate Sequence; Drug Stability; Exotoxins; Female; Immunodiffusion; Magnetic Resonance Spectroscopy; Mice; Molecular Sequence Data; Pectins; Polysaccharides, Bacterial; Precipitin Tests; Pseudomonas aeruginosa Exotoxin A; Tetanus Toxoid; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Virulence Factors

Topics: Animals; Chick Embryo; Immunization, Passive; Methods; Mouth; Pectins; Tablets; Tablets, Enteric-Coated; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination