Shousun C Szu1, Kimi F-Y Lin2, Steven Hunt2, Chiayung Chu2, Nguyen Duc Thinh3. 1. Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, USA. Electronic address: Szus@mail.nih.gov. 2. Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, USA. 3. Division of Food Safety, Department of Agriculture, Ho Chi Ming City, Viet Nam.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Published by Elsevier Ltd.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Published by Elsevier Ltd.
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