Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants

Summary

The purpose of this study is to evaluate the safety, immunogenicity, and compatibility of our Vi-rEPA conjugate administered to infants with their routine vaccinations. We propose to recruit 300 full term healthy newborns in Vietnam and randomly divide them to receive Vi-rEPA plus DTP, Hib-TT (not yet used in Vietnam) plus DTP, or DTP alone. Consent is obtained following interviews of mothers during prenatal visits, or after delivery. All vaccines will be administered at 2, 4, and 6 months. A booster of Vi-rEPA or Hib-TT conjugate will be administered at 12 months of age and reactions monitored at 6, 24 and 48 hours after each injection. Maternal and cord blood samples are collected during labor and at delivery. Blood will be taken at 7, and 12 months of age from all study infants and at 13 months from infants injected with Vi-rEPA or with Hib-TT at 12 months. The blood samples will be assayed for Vi, Hib, diphtheria, tetanus and pertussis antibodies. The levels of serum IgG anti-Vi elicited by Vi-rEPA administered to infants by the above schedule will be compared to those elicited by this vaccine in 2 to 5 year-olds in the efficacy trial conducted in Dong Thap Province, Vietnam.

Timeline

Start

2006-07

Primary completion

2008-04

Completion

2011-01

Publications

• Background Acharya IL, Lowe CU, Thapa R, Gurubacharya VL, Shrestha MB, Cadoz M, Schulz D, Armand J, Bryla DA, Trollfors B, et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report. N Engl J Med. 1987 Oct 29;317(18):1101-4. doi: 10.1056/NEJM198710293171801.
• Background Crump JA, Mintz ED. Global trends in typhoid and paratyphoid Fever. Clin Infect Dis. 2010 Jan 15;50(2):241-6. doi: 10.1086/649541.
• Background Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet. 1975 May 31;1(7918):1211-3. doi: 10.1016/s0140-6736(75)92194-7.
• Background Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, Cadoz M, Armand J. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987 Nov 21;2(8569):1165-9. doi: 10.1016/s0140-6736(87)91316-x.
• Background Kossaczka Z, Lin FY, Ho VA, Thuy NT, Van Bay P, Thanh TC, Khiem HB, Trach DD, Karpas A, Hunt S, Bryla DA, Schneerson R, Robbins JB, Szu SC. Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam. Infect Immun. 1999 Nov;67(11):5806-10. doi: 10.1128/IAI.67.11.5806-5810.1999.
• Background Mai NL, Phan VB, Vo AH, Tran CT, Lin FY, Bryla DA, Chu C, Schiloach J, Robbins JB, Schneerson R, Szu SC. Persistent efficacy of Vi conjugate vaccine against typhoid fever in young children. N Engl J Med. 2003 Oct 2;349(14):1390-1. doi: 10.1056/NEJM200310023491423. No abstract available.
• Background Levine MM, Ferreccio C, Abrego P, Martin OS, Ortiz E, Cryz S. Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine. 1999 Oct 1;17 Suppl 2:S22-7. doi: 10.1016/s0264-410x(99)00231-5.
• Background Lin FY, Vo AH, Phan VB, Nguyen TT, Bryla D, Tran CT, Ha BK, Dang DT, Robbins JB. The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region of Vietnam. Am J Trop Med Hyg. 2000 May;62(5):644-8. doi: 10.4269/ajtmh.2000.62.644.
• Background Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV, Thanh TC, Kossaczka Z, Bryla DA, Shiloach J, Robbins JB, Schneerson R, Szu SC. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N Engl J Med. 2001 Apr 26;344(17):1263-9. doi: 10.1056/NEJM200104263441701.
• Background Ochiai RL, Acosta CJ, Danovaro-Holliday MC, Baiqing D, Bhattacharya SK, Agtini MD, Bhutta ZA, Canh DG, Ali M, Shin S, Wain J, Page AL, Albert MJ, Farrar J, Abu-Elyazeed R, Pang T, Galindo CM, von Seidlein L, Clemens JD; Domi Typhoid Study Group. A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull World Health Organ. 2008 Apr;86(4):260-8. doi: 10.2471/blt.06.039818.
• Background Sinha A, Sazawal S, Kumar R, Sood S, Reddaiah VP, Singh B, Rao M, Naficy A, Clemens JD, Bhan MK. Typhoid fever in children aged less than 5 years. Lancet. 1999 Aug 28;354(9180):734-7. doi: 10.1016/S0140-6736(98)09001-1.
• Background Szu SC, Stone AL, Robbins JD, Schneerson R, Robbins JB. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals. J Exp Med. 1987 Nov 1;166(5):1510-24. doi: 10.1084/jem.166.5.1510.
• Background Taylor DN, Levine MM, Kuppens L, Ivanoff B. Why are typhoid vaccines not recommended for epidemic typhoid fever? J Infect Dis. 1999 Dec;180(6):2089-90. doi: 10.1086/315159. No abstract available.

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