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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 (−) ssa...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909895/ https://www.ncbi.nlm.nih.gov/pubmed/20668668 http://dx.doi.org/10.1371/journal.pone.0011778 |
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author | Hien, Tran Tinh Dung, Nguyen Thi Truong, Nguyen Thanh Van, Ninh Thi Thanh Bich Chau, Tran Nguyen Hoang, Nguyen Van Minh Nga, Tran Thi Thu Thuy, Cao Thu Minh, Pham Van Binh, Nguyen Thi Cam Ha, Tran Thi Diem Toi, Pham Van Song Diep, To Campbell, James I. Stockwell, Elaine Schultsz, Constance Simmons, Cameron P. Glover, Clare Lam, Winnie Marques, Filipe May, James P. Upton, Anthony Budhram, Ronald Dougan, Gordon Farrar, Jeremy Vinh Chau, Nguyen Van Dolecek, Christiane |
author_facet | Hien, Tran Tinh Dung, Nguyen Thi Truong, Nguyen Thanh Van, Ninh Thi Thanh Bich Chau, Tran Nguyen Hoang, Nguyen Van Minh Nga, Tran Thi Thu Thuy, Cao Thu Minh, Pham Van Binh, Nguyen Thi Cam Ha, Tran Thi Diem Toi, Pham Van Song Diep, To Campbell, James I. Stockwell, Elaine Schultsz, Constance Simmons, Cameron P. Glover, Clare Lam, Winnie Marques, Filipe May, James P. Upton, Anthony Budhram, Ronald Dougan, Gordon Farrar, Jeremy Vinh Chau, Nguyen Van Dolecek, Christiane |
author_sort | Hien, Tran Tinh |
collection | PubMed |
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 5×10(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.comISRCTN91111837 |
format | Text |
id | pubmed-2909895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29098952010-07-28 A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children Hien, Tran Tinh Dung, Nguyen Thi Truong, Nguyen Thanh Van, Ninh Thi Thanh Bich Chau, Tran Nguyen Hoang, Nguyen Van Minh Nga, Tran Thi Thu Thuy, Cao Thu Minh, Pham Van Binh, Nguyen Thi Cam Ha, Tran Thi Diem Toi, Pham Van Song Diep, To Campbell, James I. Stockwell, Elaine Schultsz, Constance Simmons, Cameron P. Glover, Clare Lam, Winnie Marques, Filipe May, James P. Upton, Anthony Budhram, Ronald Dougan, Gordon Farrar, Jeremy Vinh Chau, Nguyen Van Dolecek, Christiane PLoS One Research Article 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 5×10(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.comISRCTN91111837 Public Library of Science 2010-07-26 /pmc/articles/PMC2909895/ /pubmed/20668668 http://dx.doi.org/10.1371/journal.pone.0011778 Text en Hien et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hien, Tran Tinh Dung, Nguyen Thi Truong, Nguyen Thanh Van, Ninh Thi Thanh Bich Chau, Tran Nguyen Hoang, Nguyen Van Minh Nga, Tran Thi Thu Thuy, Cao Thu Minh, Pham Van Binh, Nguyen Thi Cam Ha, Tran Thi Diem Toi, Pham Van Song Diep, To Campbell, James I. Stockwell, Elaine Schultsz, Constance Simmons, Cameron P. Glover, Clare Lam, Winnie Marques, Filipe May, James P. Upton, Anthony Budhram, Ronald Dougan, Gordon Farrar, Jeremy Vinh Chau, Nguyen Van Dolecek, Christiane 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909895/ https://www.ncbi.nlm.nih.gov/pubmed/20668668 http://dx.doi.org/10.1371/journal.pone.0011778 |
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