A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children.
BACKGROUND: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
2010
|
| _version_ | 1797080332516720640 |
|---|---|
| author | Tran, T Nguyen, T Nguyen, T Ninh, T Tran, N Nguyen, V Tran, T Cao, T Pham, V Nguyen, T Tran, T Pham, V To, S Campbell, J Stockwell, E Schultsz, C Simmons, C Glover, C Lam, W Marques, F May, J Upton, A Budhram, R Dougan, G Farrar, J |
| author_facet | Tran, T Nguyen, T Nguyen, T Ninh, T Tran, N Nguyen, V Tran, T Cao, T Pham, V Nguyen, T Tran, T Pham, V To, S Campbell, J Stockwell, E Schultsz, C Simmons, C Glover, C Lam, W Marques, F May, J Upton, A Budhram, R Dougan, G Farrar, J |
| author_sort | Tran, T |
| collection | OXFORD |
| description | BACKGROUND: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile. OBJECTIVES: We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years. METHODS: Subjects were randomly assigned to receive either a nominal dose of 5x10(9) CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA. PRINCIPAL FINDINGS: One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36%) of 50 subjects in the placebo group (odds ratio (OR) [95%CI] = 1.23 [0.550-2.747]; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC(-)ssaV(-)) ZH9 was detected in 51 (51%; 95% CI, 41-61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92-99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88-100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested. CONCLUSIONS: This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children. TRIAL REGISTRATION: Controlled-trials.com ISRCTN91111837. |
| first_indexed | 2024-03-07T00:58:28Z |
| format | Journal article |
| id | oxford-uuid:88e66efa-760c-4284-a514-5d7a7a68f876 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:58:28Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:88e66efa-760c-4284-a514-5d7a7a68f8762022-03-26T22:20:49ZA randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:88e66efa-760c-4284-a514-5d7a7a68f876Symplectic Elements at Oxford2010Tran, TNguyen, TNguyen, TNinh, TTran, NNguyen, VTran, TCao, TPham, VNguyen, TTran, TPham, VTo, SCampbell, JStockwell, ESchultsz, CSimmons, CGlover, CLam, WMarques, FMay, JUpton, ABudhram, RDougan, GFarrar, JBACKGROUND: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile. OBJECTIVES: We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years. METHODS: Subjects were randomly assigned to receive either a nominal dose of 5x10(9) CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA. PRINCIPAL FINDINGS: One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36%) of 50 subjects in the placebo group (odds ratio (OR) [95%CI] = 1.23 [0.550-2.747]; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC(-)ssaV(-)) ZH9 was detected in 51 (51%; 95% CI, 41-61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92-99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88-100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested. CONCLUSIONS: This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children. TRIAL REGISTRATION: Controlled-trials.com ISRCTN91111837. |
| spellingShingle | Tran, T Nguyen, T Nguyen, T Ninh, T Tran, N Nguyen, V Tran, T Cao, T Pham, V Nguyen, T Tran, T Pham, V To, S Campbell, J Stockwell, E Schultsz, C Simmons, C Glover, C Lam, W Marques, F May, J Upton, A Budhram, R Dougan, G Farrar, J A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children. |
| title | A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children. |
| title_full | A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children. |
| title_fullStr | A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children. |
| title_full_unstemmed | A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children. |
| title_short | A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children. |
| title_sort | randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine m01zh09 in healthy vietnamese children |
| work_keys_str_mv | AT trant arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyent arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyent arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT ninht arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trann arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyenv arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trant arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT caot arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT phamv arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyent arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trant arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT phamv arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT tos arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT campbellj arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT stockwelle arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT schultszc arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT simmonsc arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT gloverc arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT lamw arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT marquesf arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT mayj arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT uptona arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT budhramr arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT dougang arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT farrarj arandomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trant randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyent randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyent randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT ninht randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trann randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyenv randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trant randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT caot randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT phamv randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT nguyent randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT trant randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT phamv randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT tos randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT campbellj randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT stockwelle randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT schultszc randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT simmonsc randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT gloverc randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT lamw randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT marquesf randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT mayj randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT uptona randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT budhramr randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT dougang randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren AT farrarj randomisedtrialevaluatingthesafetyandimmunogenicityofthenovelsingleoraldosetyphoidvaccinem01zh09inhealthyvietnamesechildren |