Six-month follow up of a randomized clinical trial-phase I study in Indonesian adults and children: Safety and immunogenicity of Salmonella typhi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine

PLoS One. 2019 Feb 13;14(2):e0211784. doi: 10.1371/journal.pone.0211784. eCollection 2019.

Abstract

Introduction: There is a high global incidence of typhoid fever, with an annual mortality rate of 200,000 deaths. Typhoid fever also affects younger children, particularly in resource-limited settings in endemic countries. Typhoid vaccination is an important prevention tool against typhoid fever. However, the available polysaccharide typhoid vaccines are not recommended for children under 2 years of age. A new typhoid conjugate Vi-diphtheria toxoid (Vi-DT) vaccine has been developed for infant immunization. We aimed to define the safety and immunogenicity of the Vi-DT vaccine among adults and children in Indonesia.

Methods: An observational, blinded, comparative, randomized, phase I safety study in two age de-escalating cohorts was conducted in East Jakarta, Indonesia, from April 2017 to February 2018. We enrolled 100 healthy subjects in 2 age groups: adults and children (18-40 and 2-5 years old). These groups were randomized into study groups (Vi-DT vaccine), and comparator groups (Vi-polysaccharide (Vi-PS) vaccine and another additional vaccine) which was administered in 4 weeks apart. Subjects were followed up to six months.

Result: One hundred healthy adults and children subjects completed the study. The Vi-DT and Vi-PS vaccines showed no difference in terms of intensity of any immediate local and systemic events within 30 minutes post-vaccination. Overall, pain was the most common local reaction, and muscle pain was the most common systemic reaction in the first 72 hours. No serious adverse events were deemed related to vaccine administration. The first and second doses of the Vi-DT vaccine induced seroconversion and higher geometric mean titers (GMT) in all subjects compared to that of baseline. However, in terms of GMT, the second dose of Vi-DT did not induce a booster response.

Conclusion: The Vi-DT vaccine is safe and immunogenic in adults and children older than two years. A single dose of the vaccine is able to produce seroconversion and high GMT in all individuals.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Immunogenicity, Vaccine*
  • Indonesia
  • Male
  • Tetanus Toxoid / administration & dosage*
  • Tetanus Toxoid / adverse effects
  • Tetanus Toxoid / immunology
  • Typhoid-Paratyphoid Vaccines / administration & dosage*
  • Typhoid-Paratyphoid Vaccines / adverse effects
  • Typhoid-Paratyphoid Vaccines / immunology
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / adverse effects
  • Vaccines, Conjugate / immunology

Substances

  • Tetanus Toxoid
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Conjugate

Grants and funding

All phases of this study were supported by PT Bio Farma, Indonesia, which also provided salaries for MP, RMS, NSB. In other way, BEM, SSu, IR, HG, RS, SK, HIS, and SRH received investigator initiated research grant support from PT Bio Farma. Additional support came from the International Vaccine Institute (with funding from the Bill and Melinda Gates Foundation), which also provided salaries for JSY, JLE, SS. These funders provided support in the form of fund, but did not have any additional role in data collection and analysis, decision to publish, or preparation of the manuscript. These specific roles of these authors are articulated in the “author contributions” section.